Wilson: “I'll start with actually my Ph.D., which is talking about bacterial antibiotic biosynthesis. And so, I did some work in that arena, but since then, I've actually been working on bacterial protein toxins. These are very potent eukaryotic modulators that when bacteria get into the host, they release these proteins that are very large, that are able to interact with very specific cells. They actually get inside the cells—into the cytosol—and then they affect various signaling pathways in the host that can go anywhere from killing the cell to modulating some of the processes that the cell undertakes, even differentiating them and causing cancer.
So, one of my main focuses in my lab has always been to understand the structure and function of these toxins, to understand how they affect the eukaryotic cell system. And then now that we know a lot about them, we're actually moving more into the direction of trying to basically use them as biologics. We have some platforms that we call bacterial toxin inspired drug delivery, where we're using the mechanisms of how they work and their exquisite specificities to be able to actually use them for therapeutic applications.”
Ho: “I got my start doing molecular genetics, actually, with John Mekalanos at Harvard, and I was kind of at the ground floor of the seminal work looking at the Type VI secretion system. And so, I got a front row seat to the kind of discovery and a lot of the initial understanding of the system. And I've kind of taken that work and expanded beyond it to look at kind of the ways different bacteria interact with each other within microbial communities. So my current work is looking at both DNA conjugation as well as the type six antagonism, and how the bacterial interactions kind of work together to build a larger population dynamics and interface with like the hosts that kind of house a your microbial communities.”
Antimicrobial Resistance
Wilson: “In 2005 [when the first edition of Revenge of the Microbes was written], there was very little activity or understanding about antibiotic resistance and how important it was. Outside of the field, doctors were encountering it. But oftentimes what was happening is they just said, ‘Oh, well, we'll just find another drug, you know.’ And pharmaceutical companies, they were recognizing that there was a problem, and they would go off trying to hunt for new ones. And then right around the late 90s, there was a big impetus, because they thought, ‘Oh, we, we have a miracle here, because we now do complete genomes. We can get out the comparative genomics and all the high throughput things, all the animations,’ and that this would lead to many more new discoveries. And I think the pharmaceutical companies were very disappointed, and they started backing out of what they deemed a huge commitment.
Two decades later, people already were starting to get aware, at least in the field, and even the industry and the physicians. People were getting aware, but I think that they were stumbling, because of their silos, in trying to get interactions with each other. And I think part of it was that they felt that, ‘Oh, we can try to solve it ourselves.’ And in reality, this is a problem that that is concerning everyone, and everyone is contributing to it. Everyone has to find a solution to help, and we need to have more synergy. There have to be more interactions, and we have to do this at a much more global scale. And so that was sort of what, what we thought when we first started the [2nd edition of the book, Revenge of the Microbes].”
Ho: “At that point, I was just starting my new faculty position, and so I started having to teach students directly. And a lot of students were coming in and giving their presentation on their research proposal or project that they have, and they very adamantly declared the reason why we have antibiotic resistance. ‘The problem is because doctors are over prescribing antibiotics.’ And I'm scratching my head—a little like, ‘Hmm, that's a really confident statement that you're making.’ Next student comes in and they're talking about, ‘Oh, it's all the farmers that are overusing antibiotics and causing the problem.’ And then the next student comes in like, “Oh, the greedy corporations or pharmaceutical industry is trying to milk us for everything, and antibiotics are not profitable enough.’ And, and I'm sitting here listening to the students who have a very narrow perspective. And clearly, they're getting it from whoever is teaching their classes.
And so, it feels like every single perspective at every single stage, they only see things through their own eyes, and can't understand what the broader perspective is and why you have all these various different problems, and I guess we call them stakeholders in the thing. It is that that every different angle has its own personal motivations. Corporations do need to have money and persist to exist. Doctors, if you encounter a patient that is dying, well, you have a moral compulsion to actually treat them. And farmers having their livestock, well, their livelihood is at stake if they don't have their animals survive, right?
And so, what I think was really important that we wanted to do is present the problem of antibiotic resistance and the way it works and why it's an issue, but also convey different perspectives on it, so that if people can kind of understand where everybody else is coming from, we can come together and have a more unified perspective, or understanding, at least, so that you're not thinking that everybody is this malicious actor, and you can actually work together to come with up with a complete solution.”
Wilson: “The first book, was very important, because you needed to get people's attention right, right? But we got the attention. So, now let's come up with a plan! And we don't have a good plan. People are making progress. People are moving in the directions that need to be moved, coming up with alternatives, coming up with, you know, even financial solutions, to some extent.
They're not enough, still, and it's going to take a global community to come forward and buy in to the problem. And I think we still have a large sector of our whole global community that are not really fully aware of what really this problem entails. They hear on the media and the news, ‘Oh, the crisis is here. We're in danger.’ And then a year later, they say, ‘Well, what happened? Nothing's happened.’ It hasn't impacted their lives yet, right? Or at least not in a way that they've noticed. And I think this is why we need more awareness. We need to get the word out there. We need to actually start having folks that make some of the big decisions, both financially, regulatory and other types of things, like education.”
Ho: “One really big problem I think that COVID introduced us to, is that it's not just that we have to convince everybody it's important, but we have to also get people, in general, the population, to trust us. You know, that there is a problem. There's been a kind of an erosion in the trustworthiness, or trust in the institutions that we relied upon that are responsible for keeping everybody safe and healthy. And I think a big part of that is also communication education, that the populace needs to be better educated, but the communication level of people in charge, as well as researchers like us—we need to speak to the people in a way that people can understand.”
Wilson: “We're not saying that we have a solution, but we do have some directions that, in many areas, have started, and we feel that they need more support. And we're hoping that folks that are reading the book actually appreciate that aspect of it, and then start realizing that, ‘Hey, I'm part of this solution too.’ It can be very little—being mindful of making sure that we have clean water, making sure that we have food security, making sure that we stay healthy and, therefore, we don't have as many infections, right? Just little things like that that we can actually do as individuals, that as a whole population, will actually contribute to improving the situation.
Then, of course, we have to support our leaders in making some of the decisions. We have to let them know that we care about this. And I think at this stage, what we're hoping is that we can maybe encourage some folks to take a citizen stand on this, to ask questions, to start going and probing and saying, ‘Hey, congress person, what are you doing about this?’ And maybe just start the dialog. This is all we're doing, is starting a dialog.”