Antibiotics are one of humankind's most amazing discoveries. Ever since that fateful day in 1928 when Scottish physician Alexander Fleming noticed a funny mold growing in one of his petri dishes, antibiotics have been kicking bacterial butt.

That famous mold, of course, was producing penicillin, the founding antibiotic superstar, which has since extended the average human life by at least a decade. It fundamentally changed the face of medicine. Antibiotics, or antimicrobials, are basically selective poisons designed to either kill or slow the growth of bacteria to the point where your body's own immune system can clean up. These drugs target a specific part of bacteria or some important stage in their development without damaging the body's host cells. And they're really great their job. Until they aren't.

Lately, antibiotic technology has been having a hard time keeping pace with bacterial evolution. We've talked here on SciShow about how lots of your die-hard, go-to favorite antibiotics are starting to lose their mojo in the face of sneaky and rapidly evolving bacteria. The US Centers for Disease Control and Prevention estimates that at least 2,000,000 Americans became infected with drug-resistant bacteria in 2012, and 23,000 of them died as a result. These superbugs are deadly serious and could quickly unleash a global health crisis if we don't find a way to keep them in check. The problem is we've already hit up many of the most obvious sources of antibiotics, like fungi, which includes penicillin, and synthetic molecules.

Fortunately, we humans have big, delicious brains, and some of the best of them are hard at work trying to invent all-new ways to kill dangerous bacteria or find other organisms on the planet that are better at it than we are so we can steal their secrets. And while they're finding some promising leads, I gotta say, they're looking in some pretty weird places. 

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You know how everyone jokes that after some big global disaster, only cockroaches will survive? Well, we recently found what may partially explain their famous, and infuriating, tenacity. Research from the University of Nottingham suggests that certain insects, like roaches and locusts, have brain tissues that are infused with super-powered antibiotic juju. The researchers found nine different antibiotic molecules tucked into the roaches' nervous systems that may be protecting them from otherwise lethal bacteria. They're all a type of molecule known as peptides, short chains of amino acids that make up proteins, kinda like proto-proteins. And these peptides are specific to the bugs' brains. They seem to be chemicals that roaches brain cells use to communicate with each other, y'know, whenever a cockroach is sitting around thinking about stuff, which I guess can happen, and although we're not sure how these peptides actually work, laboratory tests have shown that they're incredibly effective at eliminating some of our least favorite bacteria, like the most dangerous strains of e.coli, which cause gastrointestinal infections. And even MRSA, a super-resistant type of staphylococcus bacterium that can cause unstoppable deadly infections in humans, particularly in hospitals. In lab trials, these roach brain molecules killed over 90% of MRSA bacteria, without harming any host cells.

So I can guess what you're thinking: shut up and take my money! Well, hold on a sec, because we're a bit away from having cockroach brains on the pharmacy shelves. There's still loads of technical hurdles to overcome, tests to conduct, basic things we need to figure out, like how exactly these molecules work.
But roaches aren't the only hardy animals out there. Alligators are some of the Earth's most rugged beasts. They essentially live in cesspool swamps teeming with bacteria and fungus and other microbes, and more than that, they're known brawlers. Put just a few territorial 800 pound toothy reptiles together in a dirty swamp, and you will no doubt come out with some serious bite marks and bloody wounds, even missing limbs. But amazingly, what you probably won't find are any infections. This got some bayou scientists to thinking!

 Dr. Mark Merchant, a biochemist at McNeese State University in Louisiana, helped conduct a decade long study that investigated what makes alligators so unusually resistant to bacterial and fungal infection.

Turns out, it's in their blood. An alligator's immune system is largely innate, meaning it can fight off harmful micro-organisms without having any prior exposure to them. They just pop right out of their eggs ready to do battle. We humans also have some innate immunity, provided by things like our skin and white blood cells, but a big part of our immunities are adaptive, meaning we often develop a resistance to specific diseases only after being exposed to them. Which of course is not ideal all the time, but alligators get to skip this step.

Researchers examining blood samples from American alligators isolated their infection fighting white blood cells and then extracted the active proteins working in those cells. And these two included a special class of peptides which seemed to have a knack for weakening the membranes of bacteria, causing them to die. When pitted against a wide range of bacteria including drug-resistant MRSA, these tough little peptides proved to be effective killers. They also wiped out 6 of 8 strains of candida albicans, a type of yeast infection that's particularly troublesome for AIDS and transplant patients with weakened immune systems. Such compounds may also be found in similar animals, like crocodiles, Komodo dragons, and the skins of some frogs and toads. So far, lab trials have shown that gator blood can kill at least 23 different strains of bacteria including salmonella, e.coli, staph, and strep infections AND even a strain of HIV. For now, scientists are working to find the exact chemical structures at work in four of these promising chemicals and pinpoint which types are best at killing which microbes. One problem so far: high concentrations of gator blood serum have already been found to be so powerful that they are toxic to human cells. So other biologists are taking a different approach in the search for the next generation of antibiotics.

Rather than looking at other animals, they're exploring strange, new places, like cave soils and deep-sea sediments. Researchers have recently discovered evidence of promising new fungi strains living way down in hundred million year old nutrient-starved sediments in the Pacific Ocean. Everyone thought this was a near-dead zone for life, too harsh and remote an environment for something like fungi to survive in. Just a decade ago, the only living things known to inhabit such deep sediment layers were single-celled bacteria and archaea, organisms known to flourish in extreme environments. But while examining dredged up sediments from as deep as 127 meters into the sea floor, scientists found fungi of at least eight different types, four of which they successfully cultured in the lab. Some of the fungi even belonged to the genus Penicillium, which we have to thank for the development of penicillin. Now, we're not exactly sure how old these fungi are, but they are definitely quite old and maybe, more importantly, they appear to have been living in isolation for eons. If that's the case, they may have evolved specific and unusual defenses against bacteria, which, just like their penicillin kin in that famous petri dish, could end up being a new and powerful source of antibiotics.

And there's one more strategy that scientists are using, one that works in espionage as well as in medicine. And that is seeing what the enemy is up to.

While exploring life in strange new places around the world, some biologists are looking for bacteria that have never been exposed to our drugs, but still appear to be naturally resistant to them.
Wherever we find the most naturally resistant bacteria, we might also find natural antibiotics that we never knew about.

And here, one of the most promising leads is again in one of the hardest-to-reach places: New Mexico's Lechuguilla cave, a place that was isolated from all human contact until it was discovered in the 1980s.

One of the many fascinating things that scientists have discovered here is that the cave bacteria seem to be resistant to everything.
Even though they've never been exposed to us or our drugs, all of the bacteria have proven to be resistant to at least one major antibiotic, and many tend to fend off more than a dozen of the most powerful antimicrobials we have. This suggests to scientists that the bacteria have evolved to be this way because they live in an environment that's rich in naturally occurring antibiotics, ones that the germs we live with up here on the surface have never encountered.

Now we just have to find out what exactly those compounds are.
So look, I'm not going to lie to you: we have a lot of work to do. While we might discover a new super-drug lurking in a cave or under the sea or in a cockroach's head, there's a big difference between finding a substance that cleans house in a petri dish and actually putting a new antibiotic in the vein of a human patient. So the bummer is, as promising as some of these bold new discoveries may be, none of them has yet yielded an actual marketable drug.

Still, there's a long list of successful antibiotics that we've managed to derive from strange sources, starting with Dr. Fleming's rogue fungus.

So if we keep exploring strange new places and studying how other animals deal with the problems we're facing, we just might find the next penicillin before the superbugs get the best of us.

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