Good News: We’re finally finding new antibiotics

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Jordan Heath-Rawlings Forgive me if you’ve heard a story like this before, but for years now, scientists have been sounding an alarm about a global crisis that threatens humanity. Only humanity hasn’t done much about it because there’s not much money in fixing it. No, not climate change. The other one,

CLIP: The World Health Organization is sounding the alarm. It’s latest report says some of the most powerful weapons we have and the fight against infectious disease are useless because of a growing global resistance to antibiotics. And if we don’t act now, it means even minor infections could become major problems.

Jordan: That clip you just heard is from almost a decade ago. So-called superbugs have only become more resistant to antibiotics since then. If that continues, which everyone expects it to, our best weapons against disease will be rendered useless and a lot of people will die. If only despite the fact that there is much better money to be made in producing many other forms of medication, someone somewhere could figure out how to make some new antibiotics, some antibiotics these superbugs haven’t seen before and are powerless against. If only someone could do that well, then we’d have a real shot at a victory against the future of disease. I’m Jordan Heath Rawlings. This is good Newsweek on The Big Story podcast where we leave you with a little bit of light and hope as we head towards the new year. Dr. Gerry Wright is a professor in the department of Biochemistry and Biomedical Sciences at McMaster University. He is also a member of the Michael G. DeGroote Institute for Infectious Disease Research. Hello, Gerry.

Dr. Gerry Wright: Hi, Jordan. Nice to hear you.

Jordan: It’s nice to talk to you as well. And I realize I’m asking you to sum up a rather gigantic thing to start, but just so we have a baseline here, can you walk us through a little bit how some diseases today have become, are becoming antibiotic resistant? How has that happened and why?

Dr. Gerry Wright: So we use antibiotics to treat diseases caused by bacteria. And bacteria as we all know are very small. We can’t usually see them without a microscope and they divide very, very rapidly. So their life cycle is measured on the scale of minutes to hours where ours, for us to reproduce, it takes decades. And so they can go through many generations very, very quickly, and every time they go through a generation, they can gather mutations. And the other thing that they do is they actually swap genetic information with their peers quite a bit. So there’s a lot of movement of genes in bacterial populations. And when some of those genes confer resistance to the drugs that we use, we start to have the problem of drug resistance or antibiotic resistance. So antibiotics are very different than other drugs. The cholesterol lowering medication that I take every day, I will never become resistant to it because I simply can’t mutate fast enough. Whereas bacteria can mutate so incredibly fast. And so as a result, you have this constant battle with evolution and that’s at the crux of the antibiotic resistance crisis

Jordan: To put it in a way that maybe people would be familiar with. And maybe this is too simple, so please tell me, is this the same way that we are now used to getting updated COVID-19 vaccines because there are new variants of the virus as it adapts in the wild. I know it’s not quite the same thing. Antibiotics are not vaccines. But is it fair to say that that’s a basis that people can compare it to?

Dr. Gerry Wright: Yeah, it’s absolutely the same underlying principle, which is that Darwin taught us in its natural selection, genes mutate and successful genes are stabilized in populations and that’s how you end up with these situations.

Jordan: How concerned should we be right now about certain bacteria becoming resistant to antibiotics and how quickly they are doing it?

Dr. Gerry Wright: Yeah, so the answer to the first part of your question is that I’m very concerned. And so I think others should be very concerned as well. And I’ve been working in this field for about 40 years. It’s nice to remember that antibiotics have completely changed the way that we die. So before the antibiotics were part of what we used to treat disease, most of the diseases that we died from were infections. And we’re not used to this in our current modern times other than the sort of big surprise of Covid where an infectious disease sort of ruined our lives collectively across the entire globe. We’re used to dying of things like heart disease and cancer and now neurological diseases of aging and stuff. Whereas throughout the history of humans, we died mostly of infection. And when we discovered antibiotics in the 20th century, that changed everything. It changed obviously, dying of bacterial diseases like pneumonia and other infections that were very common back then. But it also enabled healthcare workers and physicians to do crazy things like do open heart surgery or you a drug that would suppress your immune system so you could have a new heart or a new set of lungs or you could undergo cancer chemotherapy and extend your life. So antibiotics really have changed all of the ways that we envision healthcare and also the way that we leave the world most of the time. But all of those advances, which happened honestly in a really short period of time through a few decades in the 20th century, we failed to keep up with it. We failed to deliver new drugs because of the resistance issue. They’re in constant demand. So that’s part of the reason why those of us in the field are quite concerned is because we have this sort of constant pressure of resistance because of the evolution in the bacteria. Again, not enough, but we also don’t have a new supply of drugs because we’re relying on the ones that we discovered 50, 60 years ago and they’re increasingly less effective again because of resistance.

Jordan: This is where at least we start to get to the good news part of this story. Can you tell me about Zoloft loin? Did I say that right? That’s the first question. And second of all, what is it? What does it do?

Dr. Gerry Wright: So you did say it right. So the Floatin is really a great good news story in that it’s among the first new about getting two technical chemical classes of antibiotics that we’ve seen in probably since the 1980s. So remember heavy metal and big hair. That was the last time we got a new drug. So this antibiotic zin, it has a very different chemical structure. It hits very interesting target within the bacteria and it really is a reminder that we can continue to innovate in this area and deliver new drugs if we have the will. And honestly, at the end of the day, the financial means to do so.

Jordan: Why don’t we have those things or why? I’ll get back to Zol Flotus in a second, but you’ve touched on it a couple of times now. Antibiotics have changed life on this planet for humans. Why did we let ourselves fall so far behind in this race?

Dr. Gerry Wright: Yeah, so that’s an outstanding question, Jordan. There’s a lot of reasons why we have failed to keep up with the bacteria and this constant evolution of resistance. Some of them are scientific. Our major source over the last a hundred years or so of new antibiotics has been going out actually to the environment, looking for bacteria that live in the soil and fungi and molds that are circulating around who have been battling with each other for hundreds of millions and billions of years. And they produce most of the antibiotics that we have come to enjoy. And many of us have heard the story of Alexander Fleming’s discovery of penicillin because a drop of mold landed on his Petri dish and he recognized that that environmental contaminant was killing the bacteria on his Petri dish. So drug companies learned from that accident and started to mine these microorganisms that live in the environment and found all these wonderful new drugs, all the mns that keep us alive. But they stopped being successful in finding new drugs this way roughly in the 1970s. So they kept finding the same old ones again. It’s easy to find penicillin again. It’s hard to find the next new drug. And so as that was happening, the drug companies sort of moved away from that source and started looking to other kinds of drug-like compounds produced by chemists. But those turned out to be pretty much useless against bacteria because bacteria, they’re highly evolved and like to of they’re sneaky as heck and they can avoid just about any kind of chemistry that a chemist can think of. So that started to happen. And then the other thing that happened was the financial model changed, and that is drug companies make a lot of money by selling me my cholesterol lowering medicine because I have to take it every day. If I stop taking it, it goes away. But antibiotics cure diseases, and so curing a disease means that you take your antibiotic for whatever, seven to 10 days and with any luck, you’ll never have to take it again. So the business model looks very different that you can either takes just as much work to find a drug that lowers your cholesterol as it does to find a new antibiotic. So you’re going to give bet on something that you have to take every day or something that’s actually going to cure the disease and then your market goes away. It’s kind of a crass way to put it, but at the end of it, that’s what it boils down to. So what happens is that the companies who invest so significantly to deliver drugs just look at the return on investment and say, well, it doesn’t make sense to be in this field anymore because we just can’t make our money back. And so you’ve got the scientific problem of where do I find the next new leads for drugs? And then you’ve got the financial problem. And that’s a perfect storm that started to hit us in the early two thousands and to the point where now it’s becoming drug companies that work on antibiotics are as rare as he’s teeth.

Jordan: Where did Zola floatin come from then and how was it put together given both factors you just mentioned

Dr. Gerry Wright: Zola Floatin is a good news story for the chemists. It’s a completely synthetic molecule that came from chemists working originally at AstraZeneca several years ago. AstraZeneca, as many of you, or many of the listeners I’m sure will know, is a well-known international drug company. And they also looked at their writing on the wall and said, we’re out of antibiotics. So they was discovered there and they spun out the antibiotics division into its own entity that was called Entasis. And they took that compound with them or that drug lead with them, and they continued to work on it, to do all the work that’s necessary to show that it wasn’t toxic, that a show was effective and had models of infection and what have you. And then it took a not-for-profit entity called Guard P, which is an interesting new advance in our field, this kind of organization that’s whose goal is not to make a profit but is simply to try and bring new antibiotics. Guard P stands for Global Antibiotic Research and Development Partnership.

Jordan: Who is it made up

Dr. Gerry Wright: Of? So it’s a really fascinating group. It was formed by the WHO, the World Health Organization and a group called DNDI. So these are the drugs for Neglected Diseases initiative and DNDI is funded by a number of public health oriented philanthropic organization like the Wellcome Trust, like the Bill and Melinda Gates Foundation and among many others and including some countries directly. So that amalgamation of contributors and sponsors together recognize that new antibiotics amounted to in neglected diseases like Leishmania for example, or sleeping sickness or these diseases that we don’t typically think drug companies will invest in because the markets are so small and so far away. So they got together and built this thing, guard p and guard P is what spent this significant amount of money and organizational networking that was necessary to run what was called a phase three clinical trial. That is a large scale efficacy and safety trial in a number of countries for this new antibiotic. So the history of this molecule is quite interesting and convoluted and has a lot of heroes and losers around along the way as it moved from a large pharmaceutical firm to a small spin out firm to having to rely on a not-for-profit to actually make it obvious that you can actually use it as a brand new drug.

Jordan: What is this drug used for currently and what is the big picture for it? What does it tell us about what’s coming and where we’re going?

Dr. Gerry Wright: Yeah, so a floatin is targeted right now for the treatment of gonorrhea. So gonorrhea is a very interesting bacterial infection. It’s caused by an organism called nyia gonorrhea, which is actually a very hard to grow bacteria in the lab. And for the longest time it was highly susceptible to penicillin. It was one of the big success stories of the discovery of penicillin in the second World war. The joke was that if you just showed gonorrhea isolate the label from penicillin, it would die. It was so sensitive. And then in the 1970s it was started to get used quite a significant amount. It became resistant to those frontline drugs. Then over the last 40 to 50 years, it’s become resistant to all the second line drugs that the infectious disease clinicians use to treat this infection. And it’s a sexually transmitted disease and a lot of it’s got some stigma with it, obviously, but it’s quite serious. It can cause infertility, it can cause ectopic pregnancies. It’s not just a giggle in the locker room kind of thing anymore. And so what had happened is we created for colloquially these strains or we selected for by evolution and exposure to antibiotics, these strains that we call super gonorrhea that are resistant to all first and second line drugs out there, which meant you can’t cure the disease anymore. So drug resistant gonorrhea meet all the sort of most wanted lists for all the big agencies out there, the WHO Centers for Disease Control Health Canada as something that we were really quite concerned about at the fact that we had no drugs available to treat this infection. And again, just to remind you, even a decade ago, we wouldn’t be even worried about this. So along comes this drug and it shows to be highly effective against these super resistant mysia gonorrhea strains and about a hundred million people a year across the globe get infected with gonorrhea. And you could imagine the pain and suffering that it causes if you can’t treat it. So this is a big good news story because we have the first new drug to be able to treat what is becoming an untreatable infection that is quite common across the,

Jordan: I had no idea that gonorrhea had become that resistant to drugs and become that serious. I heard you mention it’s not just a, I knew it wasn’t a giggle in the locker room kind of thing, but had no idea that it was kind of the face of these antibiotic resistant strains.

Dr. Gerry Wright: And it’s one of the drug resistance strains that we worry about a lot because it’s community acquired, right? So a lot of the drug resistance problems, the multi-drug resistant bacteria that we face that infectious disease clinicians are most worried about, tend to be contained to hospitals and long-term care facilities where we use a lot of antibiotics in the first place. This is a community dispersed superbug and it’s nerve wracking to have this spreading across the globe as it has. And because of the stigma associated with it, oftentimes people don’t want to go for treatment or they’re embarrassed to go. So even when they finally do manage to get to a clinic somewhere and to find out that there’s nothing to be able to treat it, it’s a terrible situation for us to be in the 21st century. So this new drug is really outstanding news for us.

Jordan: So it’s already a huge win for its efficacy against gonorrhoea. Last question is just like in the big picture, how much is it worth to the medical community, to humanity to know that with this kind of model and this kind of effort, we can stay ahead of these bacteria?

Dr. Gerry Wright: I’m hoping because I tend to be a hopeful person, I’m hoping that what this is is maybe the turning of the page to show that you can initiate programs in a for-profit situation. You can have them evaluated using funds provided by organizations that are in it for the sake of getting drugs to patients who need them as opposed to patients who are paying for them. And it becomes really important in this field, and I think this model I’m hoping is not a one-off. I’m hoping that the folks who fund guard P see this as a big success and as a way to go forward. I know that governments across the globe are waking up to the danger of multi-drug resistant bacteria, antibiotic resistant bacteria, and the impact it can have on society and our healthcare system. Most countries around the globe right now have an action plan to deal with antibiotic resistance. The unfortunate thing is most of them, including Canada, are not funding it, but there’s a plan on the paper. So that’s a step one. And maybe with examples such as this one, we could actually see that it’s not an unsolvable problem that we can move forward. There are labs in universities and in small companies and even in some pharma still full of people who care deeply about this problem who don’t want to see us change the way we die, where they go back to what it was like before antibiotics were discovered and brought into clinical use. So there’s a lot of willingness to go forward. There’s a lot of great scientific advances at this point to be able to help push those scientific problems aside and start to solve them. It just requires recognition at all levels of society that this is something, this is a problem we want to solve because we don’t want to go back to a situation where we’re dying of infections instead of dying of old age.

Jordan: And now at the very least, we have a prime example we can hang our hat on to say, this is how we do it, this is how it can be done. Gerry, thank you so much. Thank you for being so hopeful, for being so informative. It’s always nice to cover a good news story, so thanks again.

Dr. Gerry Wright: It’s entirely my pleasure, Jordan. So thanks for your interest,

Jordan: Dr. Gerry Wright of McMaster University. That was The Big Story. I told you. Good news all week, nothing wrong with that for a change. You can find the rest of good Newsweek right here in whatever feed you’re listening to The Big Story on, or you can head to The Big Story podcast.ca if you’ve got some good news to share with us or some bad news, which we’ll get back to in the new year. I promise you can let us know by finding us on Twitter at The Big Story fpn or sending us an email to hello at The Big Story podcast.ca or by calling us and leaving us a voicemail. That number, in case you haven’t memorized it the way I have, is 4 1 6 9 3 5 5 9 3 5. The Big Story is available in every single podcast player. And of course on your smart speaker, if you get one for Christmas, ask it to play The Big Story podcast. Make that the first thing it ever does. Christen it properly. Thanks for listening. I’m Jordan Heath-Rawlings. We’ll talk tomorrow.