11.21.2005

Clip Clip

So I finally got published…..even if there is absolutely no style in the piece. It’s on Science magazine’s online news site. Check it out at:
http://sciencenow.sciencemag.org/cgi/content/full/2005/1121/1

11.18.2005

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.  

11.12.2005

Can Science Save The Holy Wisdom? (And Does It Need Saving?)

So why has it been ages since Ginny has updated her blog? Well, a certain feature story (and its associated interviews and background research) about earthquakes, architecture, and the Byzantine Empire has taken most of my writing energies. Here’s the first paragraph…..perhaps more of the 4,000-word treatise will come later. Lots of love to all my bloggers! Mwa

Every year, thousands flock to Istanbul to see the church that scholars through the ages have called the most magnificent structure on earth: the Hagia Sophia. Greek for “Church of the Holy Wisdom,” in 537 AD the 180-feet-tall domed basilica became the most visible symbol of Justinian’s new Byzantine Empire. For 1,500 years, in a land notorious for political instability, the Hagia Sophia has stood tall and resilient, transforming even, when the Muslim Ottomans invaded in 1299, from a basilica to a mosque. And sitting on top of a major fault line—one that has caused no fewer than three dozen major earthquakes to shake Sophia—the monument has also survived serious geophysical instability. International teams of civil engineers and earthquake scientists are using computer models of today’s church to figure out how it has already withstood such seismic stress. But after the most recent devastating quake in 1999, head researcher Ahmet Çakmak told the New York Times: "The fault that runs closer to Istanbul is still very dangerous…The newspapers are saying we survived the big earthquake, but that's silly. It's a big mistake. What we should do is learn from this one, expect a bigger one and be prepared." If Istanbul is to be hit with a quake of unprecedented size, the big question is whether the Holy Wisdom needs some 21st century technology to—literally—back it up.  

11.09.2005

Hitting the "Maleness" JAKpot

We all learned it in grade school: Boys have a Y chromosome, and girls don’t. A genetic switch turns on maleness or femaleness. But actually, it’s not so simple. A developing embryo’s search for its sexual destiny follows a long and windy road. “I don’t like the term sex determination,” said Mark Van Doren, an Assistant Biology Professor at Johns Hopkins University, because “it implies one moment. But it’s actually a very long process.”

The process starts with the germ cells that have the unique ability to create a new organism; male germ cells go on to produce sperm, while female germ cells produce eggs. But how is the sex of the germ cell determined? In Drosophila fruit fly experiments published in the July 28 issue of Nature, Van Doren and his colleagues found that when activated by neighboring tissue, a certain chemical pathway—JAK/STAT—develops male, but not female, germ cells.

By the time a young germ cell starts down the road to sexual identity, its gonad neighbors—called somatic cells—are already different in males and females (male somatic cells express a specific gene called doublesex). And previous studies had shown that these differentiated neighbors somehow influence the germ cell’s sexual destination. As Van Doren explained, “Germ cells can’t do it on their own...they need a specialized soma” to tell them how to develop.

To find out how exactly the germ cells are influenced by their somatic neighbors, Van Doren’s team first looked at fruit fly gonads with a male germ cell surrounded by male somatic cells. In these situations, the JAK/STAT chemical pathway was always activated—that is, a specific molecule set off a chain of reactions that ended in the expression of a protein called “STAT” in the germ cell. They knew STAT was expressed because they had added molecules with fluorescent tags to find and bind to STAT proteins, in effect “lighting them up” for anybody peeking through the microscope. For the next set of experiments, this fluorescent presence would indicate germ cell maleness.

Their next step was to see what would happen to the sex of the germ cell if they broke one of the links on the reaction chain. When they inhibited JAK/STAT in gonads with male germ cells surrounded by male somatic cells, the germ cells no longer expressed the STAT protein and thus, as Van Doren said, “Male germ cell identity was lost.”

Their most remarkable experimental manipulations, however, observed the function of JAK/STAT in female germ cells. They placed female germ cells in surrounding tissue that expressed the doublesex gene (and was therefore male). These male somatic neighbors triggered the JAK/STAT pathway, telling the female germ cells to express the STAT protein. “We took a female and made it look male,” Van Doren said, “And that’s really the wow factor.”  

Van Doren and his team have now shown that activation of JAK/STAT leads to the development male germ cells and thus, a walk down the road to Spermville. But, he stressed, this doesn’t mean females take the path of least resistance. Soon the biologists will look for somatic signals that point to Eggdom instead. Whether flies or humans, though, these signals are just early signposts along the long and torturous road to true sexual identity.

11.04.2005

Meagan Got a Clip!!!

Check it out:

http://sciencenow.sciencemag.org/cgi/content/full/2005/1104/1