Interview with Dr. Steven Theriault



AMY: Hello and welcome back to SciSection! I'm your journalist Amy Stewart, for the SciSection radio show broadcasted on CFMU 93.3 FM radio station. We are here today with Dr. Steven Theriault, the CEO and chief science officer of Cytophage Technologies. Thank you so much for joining us today, Dr. Theriault.

DR. THERIAULT: You're welcome, pleasure to be here.

AMY: So, to get us started, give us a little introduction of who you are, your education, and your career background?

DR. THERIAULT: Alright, when I always look back at my career, it's always daunting. I started off as a paramedic. Once I was a paramedic, I fell in love with medicine and wanted to become a medical doctor. So, I went ahead and went to university, I did my honours degree and then I kind of fell in love with research. And from there I ended up doing my Master's degree. And then had a choice whether or not to do an MB or a PhD and I decided to do my PhD. And I finished my PhD in molecular virology within the National Microbiology Laboratory here in Winnipeg. And what I was doing in my PhD was again, creating synthetic platforms to deal with some of our most exotic viruses that we had around the world like Ebola or Rift Valley fever and created diagnostic systems for those types of diseases. When I finished my degree I was hired by the federal government to start a program which was called the Applied Biosafety Research Program in which we actually came up with mechanisms to deal with virus infections around a pandemic or an endemic - pandemic in today is a big thing. So, all of the stuff that is revolving sort of around dealing with infection agents around the world. Once I finished that or once I was working in the government, I came up with a lot of unique ideas and I found that the government wasn't really the best place to have unique ideas to push them forward. So, I stopped working in the government and I started my own company called Cytophage. And now I'm pushing these ideas that I had in the government forward in my own capacity.

AMY: That’s awesome. I love to hear about your transition from being a paramedic and then moving into maybe the medical school direction and then being deterred by research, it just shows you all the different directions you can go in just related to health and medicine.

DR. THERIAULT: Absolutely, yeah, absolutely.

AMY: So, you're the creator like you said of Cytophage Technologies, so what inspired you to start this company and what exactly do you guys do there?

DR. THERIAULT: Well the inspiration came from when I was working in the government, there was always a huge problem with nosocomial transmission in hospitals. And nosocomial transmission is where you get infected at the hospital from an organism that’s present at the hospital. And for me it was very odd that in today's society we were still catching diseases when we were going for treatment. You know we have many chemical systems that are used to get rid of organisms, like bleach. You would think that bleach would be able to get rid of everything, but in fact it actually doesn't. It kind of just pushes around a little bit and then you can get reinfected. So in looking at all of that, I was determined to try to figure out a way to actually control biologics. And I always use this term that "I like to use biologics to control biologics". Because if we use chemicals it's not sort of a natural means but if we use let's say a bacteriophage, that’s exactly what it was made for. It was made to destroy bacteria and that’s from nature. And all we do at Cytophage, and all I wanted to do, was sort of harness that power of the bacteriophage in a way that we can use it for a treatment. Now that comes with many problems again. We could talk about natro-phages and what we do to modify them to ensure that they move forward. But when you're using natural bacteriophages for treatments, you sometimes are looking for what is called a needle in a haystack. They're very difficult to find. And they're difficult to find because you want to ensure they have the attributes you want them to have so they're not going to cause problems later on down the line. And again, that was something I felt passionate about and again being a synthetic biologist, I had many ideas that we could use and that we could create new phage products to actually overcome those inherent issues that we have with natro-phages. I don't want to say that natro-phages are bad, I do want to say they're difficult to find, but when you do find them they work just as well as the pages that we create as well.

AMY: That's very cool. That’s a very unique problem you wanted to address there. I've never really heard about the dangers about recatching an infection at a hospital, that definitely seems like something we should have addressed by now. But I also like how you have the idea of targeting natural issues like infections with natural products like bacteriophages and not so much chemicals. I think that's a really good message. So for my next questions, how did the mechanisms of a bacteriophage differ from that of antibiotics, making them a better alternative? And is there still a risk of resistance like that we see with antibiotics?

DR. THERIAULT: So, we'll answer the first questions first. So, when we're looking at antibiotics, when we're using antibiotics, they're generally a protection mechanism for a bacteria or fungi or something along that line. And what's doing is it's protecting itself from that bacteria. Now resistance occurs because that bacteria is also trying to attack and get food. So, it will modify or evolve itself to get around that antibiotic. Now when we're using antibiotics in the sense of natural environments meaning a fungi is creating an antibiotic and then the bacteria can't kill it. That, you won't see resistance occurring very often because it's a very limited scope and you also have sort of a limited amount of resistances that can occur naturally. However, when we're using antibiotics in humans and using them for mass treatment, we see a huge uptick in the ability of a bacteria to create resistance to that, and we've seen this now for decades. So simply saying that using antibiotics continually in this manner is not sustainable, we've actually noticed that and we see this today. We have very few antibiotics that are new in fact I don’t think there is very many that are new that are not super toxic as well as new. So, there is a huge problem. We're also running into organisms that are so resistant to the bacteria or the antibiotics that we use that there's no more treatment, there's no more ability to use antibiotics. So, in saying all of that, looking at bacteriophage they're sort of a solution for us in two ways. So, when we're using bacteriophage and we use them to treat bacteria, we have two evolving organisms being present at the same time. So, I'm going to say something kind of funny here, but as the bacteria is creating protection mechanisms to protect itself from the phages, the phages are producing attacking mechanisms that are going to help them get into the bacteria. So, when we’re talking about resistances we have to look at sort of the resistances in that sort of capacity. Now, if I jump back and say antibiotics we'll see resistance occurring all the time because that antibiotic can't modify or change itself to meet the bacteria, it's only one structure and that's why we see mass amounts of resistance occurring. When we look at bacteriophage, we have a few things that are to our advantage. One, when we modify the bacteriophages, we can modify them in a way where resistance won't occur, meaning we remove transduction and we remove lysogeny from occurring, which actually removes the ability of that bacteriophage to mutate itself to cause a resistance, basically. When we're looking at that again, it's extremely beneficial. Now when we can modify them and remove those genes that are actually responsible for that resistance, then we don't see resistance occurring at all. In fact, in all of our products we've tested for resistance for over a year and we don't see resistance occurring to the bacteria or to the bacteriophage and the bacteria. So in saying that, we don't have an issue with resistance, but I will say that in the future we may have to deal with it. Because bacteriophage are only starting to be used for widespread treatment as opposed to antibiotics which have been used for widespread treatment for, you know, decades. So are we going to see something that is going to occur in the future, I don't know? But currently the science is showing that resistance doesn't really occur at that capacity that antibiotics was occurring because of these inherent sort of mechanisms that bacteriophage can modify themselves against the bacteria.

AMY: That’s exciting to see that this might be a really good prospect for targeting the issues that antibiotic is kind of failing to. And even though you said there might be a chance where resistance can pop up again, it seems like the bacteriophage is a lot more dynamic and you can work with them a lot more versus a lot more static in antibiotics. So, what are some potential applications of bacteriophages and what are you guys hoping to do at Cytophage with them?

DR. THERIAULT: Oh boy, so, this is the thing I love about synthetic biology and I love about bacteriophage, is the sky is the limit right now. So for us, when I started the company in 2106, I was a human health guy. I really wanted to combat nosocomial infections and I went straight to the hospital with bacteriophages for clostridium difficile, MRSA, VRE, so these are organisms that are causing a lot of the nosocomial issues that we have in hospitals. And again they're really bad organisms, you don't want to catch them. So when I was first starting the company, I really wanted to work on these organisms but then reality hit in when I tried to go to a hospital and say "okay I have these phages that can get rid of C. difficile and now I have to do human trials'' and they say "well yeah, sure human trials" you look it up it cost about 40 million dollars, like it's just, I'm just throwing out that number, it's a huge number, And for a small biotech company, it was unsurmountable, meaning that it was something we just couldn’t do to prove out phage technology. So, what we did was, it's kind of ironic that it happened. I was having a chat with my neighbour, I live in southern Manitoba, so I live in a ruraler area and my next door neighbour is actually a chicken farmer. And we were having a good conversation and he basically said "well I'm getting out of the business I'm not longer going to be a chicken farmer because antibiotics can no longer be used prophylactically in our chicken farms" which again is a really good thing but a not a good thing when you're trying to protect your animals from disease. And he said the government doesn't have a viable solution. We had a chat, I told him what I was doing, creating phages and I basically jumped the fence and moved into agriculture and dealing with the animal sector. And the reason I did that was because the data that we accumulate with phage treatments is immense, meaning I'm treating 15 000 chickens every 30 days, we're seeing a lot of good data, data coming out, showing us exactly how we can use bacteriophages productively. The other cool part was, I gave him a solution that actually allowed him to keep his chicken, birds, or his farm healthy, as opposed to when he wasn't using antibiotics, sometimes he would be fine, he would have no issues but other times he would lose his entire flock. So again, there was issues that have sort of come up with the use of antibiotics that they've been using for such a long time, that we won't see with the bacteriophage. So, that’s sort of why I jumped the fence and went into the animal market and honestly it's been a very good market, meaning that we have a product now for salmonella, we've tested it, it stops transmission of salmonella over 50% when we give them a very, very high dose of the bacteria. So it's a very good treatment, and then we're moving into mastitis for cows and of course we're doing a lot of stuff in swine. So that's one aspect of the company. And the reason we're doing that is because again we're collecting all of that valuable data that we can use for the regulators to get our products approved for other types of use. Now there's another aspect that we're using bacteriophages for and that stems from my experience again in working in the government as an infectious disease scientist and seeing that with Coronavirus we have a huge opportunity, I guess. When we're using vaccines, I'm going to jump around a little bit, but when we're using vaccines, the mRNA vaccines again are very effective, they produce a nice IGG response and IGM response giving you protection within your blood system against the disease. Now this will protect you from lethal disease but it doesn't protect you from catching the virus or transmitting the virus. So what we did instead with the bacteriophages, because we can synthetically manipulate them, we've taken the SPIKE protein of the Coronavirus and put it on to the surface of a bacteriophage, so the actual head of the bacteriophage is presenting the SPIKE protein. We've modified the bacteria so it resides in your mucosa and when it resides in your mucosa we’re stimulating the antibody IGA. Which actually protects you from catching the virus and transmitting it. Now we're doing animal studies right now and we're getting, again, very good results, but we're using a bacteriophage in an entirely different mechanism. We’re actually using it as a delivery system to stimulate your immune response. And this has opened up a broad range of things that we can do with phage. Bacteriophaging and phage display is not new, but because of the modification we can do for it, it's given us a huge advantage in developing cures that are cheap to grow, non-toxic, meaning again no issue with toxicity at all, and very effective. So, as we're sort of bringing this technology forward, you'll see it in the next couple of years, a lot of people will move to using these types of organisms for vaccine production as opposed to animal viruses.

AMY: That is some very exciting work you guys are doing there. I think it's going to have a really big impact on the agricultural industry and I mean the work you're doing with COVID I think that's just amazing that you're able to stop it, not be able to transmit it or even catch the disease. I think that’s absolutely the best solution because then nobody gets it. That’s really cool what you guys can do with that and not what I was expecting at all, very cool.

DR. THERIAULT: Yeah it’s a growing project and yeah we're again working with the government to fast track it in the sense to make sure that it's effective and then once it's effective, we just have to do the rest of the animal work to show that there's no toxicity, which we already know there's no toxicity. But then we can start using it as a treatment. And I foresee that this treatment would be used not only for like Coronavirus, you know it's petering out, hopefully it can be used for Coronavirus. Our biggest goal is to actually help with flu and creating a universal flu vaccine, and that could be done on this template because I can put eight different epitopes on this particular bacteriophage, that means eight different binding sites for your immune system to respond to create antibodies.

AMY: That is very exciting, especially with how tricky it is to target the flu and the guess that some scientists have to take when they're creating the vaccine. It's very exciting that there is going to be potentially a solution that could just stop it right from the get go. So for my final question, as a scientist, a researcher, a teacher, a company owner, what advice would you give to undergraduate students who want to pursue just a career in science?

DR. THERIAULT: You know, I have a lot of students that come through my company as well as that I mentor. And what I always tell them is to keep an open mind, when you’re looking at science you have to be subjective of the science. And I always like to see students that have a question and then when they answer that question, they have ten more questions. And that’s what being a scientist is, it's having that excitement behind learning something new, and dealing with things that are absolutely different. But if I can give you some advice as being a scientist, I would say make sure you think out of the box. Because if you don't think out of the box then you’re going to be confined by it, and if you're confined by it then you're not going to come up with anything that’s unique or different. You're going to be stuck in your box and you know the other part of that, for upcoming students, communicate with professors like me, or business owners like me. I find that also students are very tentative to have that conversation. Which is again not useful for them and we as professionals in the field are always open to discussing things with people who are upcoming. And just again, be open and have that discussion and be part of it, as opposed to hiding somewhere else and not sort of having that discussion.

AMY: That’s some really great advice and I can see you definitely live by that curiosity. I mean from what you’ve described our career has been like different interests coming up and you just going to pursue them and I think that’s definitely the way to do it. I mean look where you're at now, you're doing some really amazing work.

DR. THERIAULT: Thank you, thank you.

AMY: And I have to agree with the communication aspect too. Because as an undergrad student myself, sometimes it is intimidating to contact your professors especially if you just want to talk about their work and research, but sometimes it's the best way to find out about different directions of where you can go in sciences.

DR. THERIAULT: Yep, it's funny I'm a CEO of a company, my schedule is ridiculous, but I will always take 15 minutes out to have a coffee with a student just to discuss science and having a conversation as two individuals, is amazing, especially when you have different opinions.

AMY: That’s a very great perspective and I'm sure students all around are very grateful for that. Well thank you much for joining us today Dr. Theriault. It was amazing to hear about your career and the conception of your company. The work you are doing at Cytophage is so relevant and important, and I'm excited to see what comes next.

DR. THERIAULT: Thank you it was a great pleasure to be here.

AMY: That’s it for this week of SciSection! I'm your journalist Amy Stewart and make sure to check our podcast available on global platforms for our latest interviews.