Finding New Bugs in an Old Broth

Charles Dickens gave it to Tiny Tim; Hippocrates described it as the most widespread disease of his day; paleontologists even found traces of it in 5,000-year-old Egyptian mummies. Tuberculosis is an old disease. And the diagnostic tests for TB, in contrast to the “cutting-edge” progression of most medical technologies, are similarly ancient. The majority of the world’s hospitals use a “sputum smear test” that has remained unchanged since its invention in 1881: your suspect phlegm is placed in a glorified Petri dish of nutrient broth, where the lung-eating bacteria can grow, though very slowly. After many weeks, when they’ve grown into visible clumps, a microscope can identify the killer bug. But to how many will you spread it while waiting for test results?

Tuberculosis diagnosis, “is as old-fashioned as it gets,” says Dr. Richard Chaisson, the founder of the Johns Hopkins Center for Tuberculosis Research. Faster, cheaper and more accurate diagnostic tools are desperately needed, Chaisson says, to curb the growing epidemic of TB—a curable disease that still kills 5,000 people every day. This summer, three biotech companies announced partnerships with FIND, the Foundation for Innovative New Diagnostics, to develop better TB-testing products. But a large-scale study is about to be released suggesting the most effective diagnostic method is not a product at all, or at least not a patentable one. It’s just a new way of looking at an old broth.

The global TB crisis made U.S. headlines on October 17, when pharmaceutical kingfish Bayer announced it will allow one of its best-selling antibiotics to be tested against tuberculosis. Chaisson, who was instrumental in the deal, says the drug will reduce treatment time from six months to four. Still, he has reservations about its effect on the epidemic’s spread through the population. “The individual cure rate is awfully good,” he says, “but the number of cases is still going through the roof.”  This is partly because of the increase in HIV infections; those with HIV have compromised immune systems and are thus more vulnerable to TB. But it also stems from the bug’s ability to adapt: strains have evolved that are resistant to every major antibiotic. Because TB is often spread more quickly than it is identified, Chaisson says the answer lies not in faster drugs, but faster diagnostics.

Today’s sputum smear test takes far too long. In Sub-Saharan Africa, where both TB and HIV run rampant, patients can expect to wait 12-16 weeks for test results, according to FIND. And the sputum smear has other problems, too. Making the broth requires electricity—unavailable in most clinics of the third world—for mixing and refrigeration. Moreover, it can’t reliably detect the presence of multi-strain TB.  

Since 2003, FIND’s mission has been to tackle these problems. This summer, three international biotech companies announced financial partnerships with FIND to develop new tests that use color-changing strips or simple test-tube reactions to detect proteins that are found in many strains of TB, getting results in hours or even minutes. One promising product is called “TK medium.” When the medium, a red substance, is mixed in a test tube with active TB bacteria, the color turns green. “Nobody knows yet why it works,” Chaisson says. “They’re about a buck each, and you could sell tens of millions of them a year.”

But no fancy new products are needed for what seems to be the best test of all. In the early 1990s, a lab tech in Peru noticed that TB bugs can be detected—using a common broth medium and a regular light microscope—weeks before the bugs grow into visible clumps. Chaisson finds it remarkable that no one had thought of the method—now called MODS—before. “The only drawback,” he says, “is that it’s not patentable.” So for now, FIND won’t fund MODS.

Compared to most bacteria, the growth of TB bugs is interminably slow. And according to Chaisson, slow too is the technological progression of its treatment and diagnosis. He describes, with obvious disdain, the conventional wisdom of most TB doctors: “My god, if it was good enough for my grandfather, then it’s good enough for me.” So perhaps MODS—using old tools and an old broth—is exactly what’s needed to unite the old and new medical philosophies, to keep the bug from staining future pages of human history.  

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