Some other Nobel winners InsightCity readers will recognize as people who’ve made all our lives better are the recipients of the Nobel Chemistry Prize. One half of that goes to Frances H. Arnold, who was the first to use directed evolution to speed up the production of useful enzymes. Arnold becomes the fifth woman to win a Nobel Chemistry Prize, so hopefully they’ll soon catch up with men named John, who currently have seven between them. The other half goes to George P. Smith and Sir Gregory P. Winter, who used bacteriophages to do that directed evolution thing. Quick tangent, bacteriophages are kinda creepy but also may be our last defense against antibiotic resistance. Both discoveries have led to new compounds for use in “everything from renewable fuels to pharmaceuticals.”
Bacterial alcohol resistance:
Source: Science Translational Medicine
Quick science lesson: there are two types of bacteria, known as gram-positive and gram-negative, that have different cell wall structures. This has presented issues for those who develop antibiotics, as the two types can mean that medicines which target one are ineffective against the other. What do you do when two kinds of walls won’t let invaders in? Build a double trojan horse, of course, of course. Clever war strategists/scientists attached antibiotics to the molecules that bacteria send out to gather iron. Once those molecules find iron and head home to their bacterium, the cell walls willingly accept the molecule, antibiotic included. But sometimes bacteria can still destroy antibiotics with enzymes, so the “double” part of the analogy kicks in—the act of destroying the first antibiotic releases the second. That’s a pretty hardcore Catch-22.
Antibiotic resistance is one of the most urgent issues affecting healthcare, costing thousands of lives and billions in medical costs each year (click here for the CDC’s list of the scariest strains.) It’s an annoying problem. R&D produces a new antibiotic and within some years the little buggers have already figured out how to not get killed by it (very sick video of that process here.) Well at least we have a new weapon that they might have some trouble fighting against. Malacidin is a distant relative of a newer antibiotic called daptomycin which up until now has evaded bacterial resistance. While discovering a new antibiotic is immediately cool and helpful, discovering a class that can avoid being useless after its introduction would be huge.
You know all those dang bacteria in your body, living there without permission, without even one of the 3.9 x 1013 of them offering to contribute to rent? Turns out about 1 in 9 of those freeloaders can neutralize gemcitabine, a pancreatic cancer drug, before it gets to work on cancer cells. While that means killing those bacteria results in a non-inhibited drug delivery, it’s not a great solution. Not only do some cancer drugs depend on the presence of other, benign microbes in your body, but using antibiotics could lead to resistance in those bacteria. And the only thing worse than bacteria-filled tumors are antibiotic-resistant bacteria-filled tumors. Hey, at least now we know what the problem is.
Here’s the scenario: Scientist A says, “We have to do something about these superbugs before they kill us all!” Scientist B responds, looking up from a Spiderman comic, “Too bad we can’t just design some super-spiders to fight them with.” And that’s where it all started. Australian researcher Sónia Troeira Henriques and her team published a study wherein they redesigned a peptide from a Brazilian spider and found that their work increased the molecule’s antimicrobial and anticancer properties. Innovators have been looking for alternatives to the existing field of antibiotics, which are becoming dangerously ineffective at combating increasingly resistant bacteria. Earlier this year, the WHO released their list of “priority pathogens” that we really need to get some stuff in the pipeline for.
Slight paraphrase, but the point holds. This week, WHO released its rapidly (tragically) expanding list of “super-bugs”—drug-resistant bacteria that have stopped responding to antibiotics. For some context, these strains resulted in more than 50,000 fatalities last year. The older and infirmed are usually at greatest risk, but five-alarm bells are sounding from new findings that pediatric infection has increased sevenfold within the decade. With our last lines of antibiotic defense now losing efficacy, the fix comes down to R&D. However, new antibiotic discoveries are limited after 70 years of research, and…pharma doesn’t get huge ROIs from antibiotic research. But Pharma, hear us at InsightCity—if anyone is saving the day, and all of humanity—it will be you.