| Happy Friday, Dailies. It was not that long ago—at least when framed against the great history of this nation—that infections were the biggest killer of Americans. In 1907, the two leading causes of death in the U.S. were not heart disease and cancer as they are now, but rather tuberculosis and the brutal duo of pneumonia & influenza (which have long been grouped together as a category). No. 4 on the list was diarrhea and its related conditions. What largely changed that—and vastly extended our lifespans in the process—was the advent of antibiotics, which came into widespread commercial use in the 1940s. "Antibiotics, as one scientific journal editorial sums up, "are arguably the most successful form of chemotherapy developed in the 20th century and perhaps over the entire history of medicine." Most of us in the developed world simply can't imagine a life in which an endless array of infectious diseases runs unchecked, decimating life around them. We have taken this for granted because, well, we have taken antibiotics for granted. The problem is, we have used this form of chemotherapy so much (and with so little restriction) that it has led to pathogens that no longer yield to it. The reasons for this are lengthy and complex, and I won't get into them here. But consider just one familiar aspect of the modern antibiotic-resistance cascade: A person comes into a doctor's office or hospital with a potentially aggressive infection, but it's not clear right away what's causing it. So the doctor, often having little choice, prescribes a so-called "broad-spectrum" antibiotic that works against a range of microorganisms—from Gram-positive bacteria like "staph" (staphylococci) and "strep" (streptococci) infections to Gram-negative bacteria like E. coli. In scenario 1, the drug works: End of story. In scenario 2, the infection worsens over the next 48 hours. The patient is scared. But by then, the specific type and strain of bacteria causing all this nastiness has been identified by culture and the patient is given a specific and powerful antibiotic to halt the colonizing germs in their tracks. It does the job, thankfully. Hugs and kisses all around. In scenario 3, the infection accelerates and the more specific, second- and third-line antibiotics have little effect because the underlying bacteria causing the infection, though now-identified, are resistant to multiple drugs. That's a not-so-happy an ending—and, unfortunately, it's getting more common than ever. But here's the rub: It's not just scenario 3 that has become increasingly dangerous. There's actually a dark side to scenarios 1 and 2 as well. Here's why: While broad-spectrum antibiotics have prevented innumerable deaths in people with serious and aggressive infections, such as meningitis (where a delay in treatment could mean the patient dies), they've also led to widespread antibiotic resistance. (I've written about the problem here—and I'll come back to this topic in-depth in another column soon.) For now, though, there's a bit of good news to share. A Boston-based startup called Day Zero Diagnostics has been developing a test that can identify a patient's specific infection-causing bacterial strain, along with the characteristics that might make it resistant to known antibiotics, within hours rather than the standard two days or so. DZD, which is cofounded by an infectious-disease doc at Mass General, Harvard, and MIT (and which raised $3 million in seed financing in August from angel investors Golden Seeds and VC firm Sands Capital Ventures), uses whole genome sequencing in combination with machine learning to rapidly identify the pathogen. What that means, conceivably, is that doctors could skip—or, at least, significantly shorten the duration of—the broad-spectrum antibiotic and go right to the drug that has the best shot of working on that specific strain. That could not only help patients (by getting them on a more targeted therapy from the start), but also reduce the evolutionary selection pressures that lead to antibiotic resistance. DZD isn't alone in this effort. Other companies are also working on shortening the ID-ID ("infectious disease identification") time—and heck yes, I'm trademarking that! But DZD just got a big boost this week by winning a prestigious medical technology "Shark Tank" competition—which as Daily readers will recall is one of my happy obsessions (see stories here and here ). "It was a pretty thrilling finale to an eight-month competition," says Paul Grand, the CEO of MedTech Innovator, who awarded the $350,000 grand prize to DZD. Beating out three finalists and nearly 600 other startups in total, it was crowned champion in a live vote by the conference's nearly 1,500 attendees. The sheer number of companies vying for a win, of course, suggests a different kind of evolutionary selection. But this one, I'm happy to say, we can live with. | 
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