But what if you could create a chemical that killed bacteria, but neutralized itself into harmless natural molecules after it did its job? USDA is trying to do ...
Modern disinfectant products work really, really well at killing disease-causing microbes. But they bring problems along with them, from possible long-term environmental damage to antibiotic resistance. But what if you could create a chemical that was just as good at killing bacteria, but neutralized itself into harmless natural molecules after it did its job? Researchers at the Agriculture Department’s Agricultural Research Service think they may have done just that. William Hart-Cooper is an ARS research chemist in Albany, California. And for his work on those biodegradable disinfectants he’s been chosen as a finalist in the Service to America Medals Emerging Leaders Category. He talked with Jared Serbu about why ARS is interested in disinfectant research and what his team has developed so far, on Federal Drive with Tom Temin.
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William Hart-Cooper: Disinfectants are part of a broader category of antimicrobial agents and antimicrobial agents are critical to many, many aspects of our society. You can’t have surgery without antibiotics. Food sanitation and the sanitation of services related to germ theory have saved so many millions of lives over the past 100 years since that understanding was developed. And right now there’s a really big challenge that’s facing us. And that’s the threat of antibiotic resistance. So currently, antibiotic-resistant infections kill about 700,000 people per year. It’s predicted that if you extrapolate current trends, antibiotic resistance will become a major problem, possibly killing up to 10 million people per year by 2050. And part of the problem there is that the more you use these miraculous chemicals, the less effective they become. So microbes have an ability to – evolve resistance to them and to become less effective. And so in order to maintain our current standards of living, and this type of technology, we need to be on that treadmill, we need to be creating new antimicrobials. And we need to create ones that are less likely to cause resistance.
Jared Serbu: Beyond the resistance issue, though, right, there’s there’s also environmental harm problems with conventional disinfectants. Right? Can you talk about some of those specific problems with the products that we have on our shelves in our in our kitchen cupboards right now that you’re trying to solve?
William Hart-Cooper: Sure. So every chemical has hazards. And hazard can be a very complicated thing to define. Typically, there’s 16 to 18 different hazard endpoints that would include things like does the chemical cause cancer? Is it a mutagen? Does it cause skin irritation? Does it cause reproductive effects? Is it toxic ecologically? Is it toxic to fish and small crustaceans and things in the natural environment? Antimicrobials and really anything that’s biologically active, including pesticides as a broad class, it’s very, very hard to have selective toxicity where you want it. They’re always going to have off-target effects and other hazards. I’ll go through two examples of antimicrobials that are used in everyday products: One of them is a classic chemical called isothiazolinones. Now, I’ve had a lot of experience with these – I’m prone to allergic skin reactions. But they are fantastic molecules at keeping formulas sterile. They’re very, very good at keeping your soaps, your shampoos – even water in some cases – free from growing pathogenic disease-causing bacteria, mold and yeast. They’re extremely potent, and you hardly even notice they’re there. You add a tiny, tiny little drop in a big formula and they work like magic. The problem is the same mechanism that causes their toxicity to microbes also, in some people, cause your immune system to react in same way. And so you can get these allergic skin reactions especially when it’s applied to skin surfaces. And the more you apply it, the more sensitized you’ll become. And people have varying sensitivities to this. But that’s one example. So that’s a common preservative used in nearly all non-food liquid products, home care and personal care products that can cause allergic skin reactions, skin sensitization. And so developing alternatives to that that don’t cause the irritation, super important. Another example of this type of chemical or quaternary ammonium compounds. Now, those are sort of the workhorse standard chemicals for disinfecting surfaces when you can’t when you can’t use bleach or oxidants or acids. You know, you don’t want to be putting bleach or oxidants or acids on your skin or on sensitive surfaces. So you use these chemicals that are relatively inert and less likely to cause irritation in that way. So that’s great. They’re used a lot in disinfectants. They’re used a lot in medical industry, food industry. They’re even used as conditioning agents, they make your skin and hair softer, so they can use your hair conditioner, or in your lotion. There’s a lot of different types of quats but the ones that are more biologically active have major issues around their ecological toxicity. They’re highly toxic to aquatic organisms in particular, like small crustaceans that might be sort of the base of a lot of aquatic food chains, and fish- especially young fish. That’s a big issue and the other issue is that these chemicals can be fairly persistent in the environments. They can linger around for, in some cases it’s been reported hundreds of days with no visible degradation, especially under low oxygen environments. And once microbes are exposed to these chemicals, they develop defenses against them. They develop what’s called efflux pumps. So these little machines that spit out the chemical. The problem is, once they develop resistance to that, once they are able to spit out this chemical, they can spit out other clinically important chemicals like clinically relevant antibiotics. Those same pores that spit out the quaternary ammonium compounds can spit out antibiotics, and it can make that bacteria resistant to it. Even if that bacteria isn’t a disease causing bacteria, those genes that encode that new invention from the bacteria, the pump can be transferred to bacteria that cause disease in people. Using these common commercial products can be something that it can lead to antibiotic resistance to develop in a broader population of bacteria.
Jared Serbu: And I think one of the root issues here, right, and tell me if I’m getting the science wrong is that these these more traditional compounds just don’t break down in water kind of ever. And I think the stuff that you’re working on does, that’s sort of the whole point. Right? So talk us through some of your solutions to all the challenges that we’ve been talking about.
William Hart-Cooper: Yeah. So I think one of the big challenges is, you don’t always have control about where your chemicals are going to end up when you’re done using it. But one thing that you do know is that it’ll probably be washed down in water, and it’ll end up in an aquatic source. Now, once it’s an aquatic source, it could partition to soil. And the picture gets a little more complicated there. But our strategy here was to look at this structure and identify the function of these molecules, and start to incorporate little reversible bonds within that molecule, so that it could unzip once it’s diluted in water, there’s a lot of different bonds that you could consider for this type of solution. A lot of them come out of the field called self-assembly. And so you can start to construct analogous compounds that resemble these chemicals, but contain that little zipper bond, that little deactivation switch that’s sensitive to a certain concentration and dilution of water. And so once you use the compounds, it gets diluted. At a certain point that’s specific to the bond that you’re using, the water will unzip it, break it apart into the subcomponents that are pre-selected to be non-toxic and non-persistent. So you can measure them in the laboratory and identify how long they last and how quickly they’re broken down by common environmental bacteria.
Jared Serbu: So if water is the reversing agent for these bonds, I assume the product itself cannot be water based. So what does the product actually look like in real life, once we get to a usable product, and how do you apply it to a surface?
William Hart-Cooper: So the nice thing about the approach is that there’s lots of possible solutions. And we’ve developed a few of them. But there’s plenty more that can be built upon this. So you can select bonds that are highly sensitive to water or less sensitive to water. One of the ones that we started out with – we wanted to match the performance of traditional disinfectants and traditional antibiotics. That means we want to retain activity down to parts per million level. So that’s one part of our compound per a million parts of water. So that’s a relatively stable reversible bond. And the way we did that, we chose one component called cuminaldehyde. That’s the smell of tacos, basically, it’s the active ingredient and cumin seed oil. So very nontoxic food grade, a lot of us consume it every day, and not toxic to the environment. The second component we chose was actually synthetic compound called aminoguanidine that shares the same functional group as found in the amino acid arginine. What’s special about it is it has a special nitrogen-nitrogen bond that gives us that stability down to parts per million levels. And so it links up with cuminaldehyde, that compound is your active compound and then once it gets diluted to a pretty large extent, and is allowed to reach equilibrium, it’s back to the subcomponents that are then biodegradable and nontoxic. And functionally they’re different than the active compound. So our hypothesis is that it’s not going to cause resistance in the same way.
Jared Serbu: As far as effectiveness in that antimicrobial action, how much do we know so far about how well the – you know a cumin seed-based oil will work compared to the Lysol that we have in our bathrooms?
William Hart-Cooper: The performance is very good. So for the active compound that has the cuminaldehyde, linked up with aminoguanidine. We call that compound a cuminaldehyde quantal hydrazone. And the testing we’ve done so far, we’ve tested it in lots of different home and personal care products. There it tends to match or surpass the performance of a lot of traditional preservatives and disinfectants. It’s the activity and how quickly it disinfects a surface is comparable to a lot of the traditional compounds because it’s functionally various similar. Like we looked at and studied the structures of existing compounds, and then we replicated it with just that reversible bond, which doesn’t impact the efficacy as long as it’s held together, as long as you don’t dilute it too much, and wait for it to break apart.
Jared Serbu: Got it.
William Hart-Cooper: Yeah, activity is similar.
Jared Serbu: Is there a path to commercialization that you can clearly see here? And do you know how you would do that at this point? And how long it would take?
William Hart-Cooper: Yeah. Well, with any new ingredient that has biological activity like this, you need to do a lot of work to show that it’s safe first. We’re pursuing multiple paths. So we’re working with partners in home and personal care industry. And at the same time, we’re exploring other applications like where else is this useful? At its core, it’s a substance that’s naturally derived, very nontoxic to skin, breaks down to nontoxic biodegradable subcomponents in the environment. And so one of the applications is, as a treatment for digital dermatitis, which is a disease that affects a lot of hoofed animals, cows, sheep, even elk. They can get these painful ulcers and lesions on their feet that are very – their hooves, they are very, very hard to heal. It’s a lot of different bacteria all mixed together, very persistent, easily spreads in feed lots. It can be very expensive and it’s just, it’s just kind of sad too, that the animals would have to live with that. And so one of the things we’re looking with is we’re developing formulas, little hoof bombs that heal those ulcers. And so far, the results have been extremely promising even after one or two applications you get complete recovery. It looks like a new hoof. And so that’s one area, we’re really excited about. Alternatives to topical antibiotics, things that can be applied to infections on skin surfaces, and that can promote healing there.
Jared Serbu: Is it still something you would classify as an antibiotic? Or is it really a disinfectant? Or is there not much difference between the two functionally?
William Hart-Cooper: It depends on the application and what claims you’re trying to make and the product that you have. If you’re claiming on your product that it eliminates 99.9% of bacteria within 10 minutes, then that’s more of a disinfectant claim. If it shows that it keeps the formula sterile over the course of two years, that’s a preservative claim. If you’re doing some sort of wound healing and acceleration of the recovery process for skin infection, that’s a different claim on its own. I think we usually talk about it as an alternative to antibiotics. It’s a new compound, it isn’t an antibiotic, which are typically isolated from bacteria, often that are grown in the soil. And they’re these miracle substances that can cure infections inside and out. A lot of times although there are topical antibiotics, this is a new molecule that we invented, that is an alternative to antibiotics and allows you to heal the animals that you have that are sick and achieve all these other applications preservative disinfection, any type of antimicrobial application that we can observe that it works, but it allows you to not use those traditional antibiotics.
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Jared Serbu: Billy Hart-Cooper is a research scientist with the Agricultural Research Service in Albany, California. To hear this interview and the rest of our conversations with his your Sandy’s finalists, go to federal news network.com slash federal drive.
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