finding new bugs in old broth

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