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  Livestock production in densely populated areas has contributed to the spread of new infectious diseases around the world, say Columbia scientists.
Disease catchers

New diseases seem to have cropped up with frightening regularity in recent decades. Consider AIDS, Ebola, West Nile virus, SARS, and avian influenza. Are we becoming more vulnerable to strange illnesses?
An international team of researchers has conducted the largest analysis of emerging diseases to date and confirmed that humans are increasingly at risk. The researchers, among them Columbia geospatial data expert Marc Levy, examined medical literature published between 1940 and 2004 and counted 335 new infectious diseases. The rate of new diseases quadrupled during that period.

The increase resulted primarily from human encroachment into wilderness areas, the researchers say. Rapid population growth caused large numbers of people to move into regions of India, China, sub-Saharan Africa, Germany, and southern England that are relatively warm and get lots of rainfall. These areas tend to be rich in biodiversity and to breed many pathogens. The majority of the new diseases are caused by bacterial and viral infections that spread from wild animals to humans.

“As people move into wilderness habitats, wild animals are being crowded into smaller areas and mixing with people,” says Levy. This has enabled diseases like SARS, which is believed to have originated in bats, to jump to humans. Large-scale livestock production in densely populated areas is also dangerous, likely explaining the spread of avian influenza in Southeast Asia, says Levy.

In order to identify the global regions that are most susceptible to emerging diseases, the scientists pulled off a sophisticated trick of data analysis. First, they plotted where all of the 335 new diseases were detected. But there was a problem: Emerging diseases tend to be identified in cities with the best medical resources, such as New York, Los Angeles, London, and Tokyo. To control for this reporting bias, the researchers considered the home institution of every scientist who wrote a paper in the prestigious Journal of Infectious Diseases since 1973.

“That gave us an idea of every country’s ability to identify a new infectious disease,” says Levy, who is associate director of Columbia’s Center for International Earth Science Information Network (CIESIN), which is part of the Earth Institute. “Then we were able to accurately measure the impact of other factors, like population density and biodiversity. Those two factors ultimately proved most important in determining a region’s susceptibility to emerging diseases.”

There were other causes: About 20 percent of the diseases resulted from microbes that became deadly in part as the result of overuse of antibiotics, the researchers reported in the journal Nature earlier this year. The data also revealed a peak in the 1980s, which Levy says likely was related to AIDS, which made people vulnerable to additional diseases. “You had millions of people suddenly with suppressed immune systems,” he says. “So a bunch of new diseases took root.”
For the project, Levy analyzed global census information that CIESIN has collected; his collaborators at the Zoological Society of London and the New York–based Wildlife Trust examined the medical literature. The paper’s coauthors include CIESIN researchers Deborah Balk and Peter Daszak.

The scientists hope the findings will prompt Western nations to give more aid to developing countries for disease-detection systems. “At a global level, we need to redistribute resources for disease monitoring to places like Southeast Asia, Nigeria, and the Congo,” says Levy. “That’s not happening right now. But if rich countries help the poorer ones, diseases might be spotted before they become devastating.”

—David J. Craig


Mending hearts

To understand how the heart works, scientists often conduct experiments on small pieces of heart tissue kept alive in petri dishes. Because these so-called heart patches are flat strips, not muscular chambers that pump fluid, scientists can learn only basic characteristics of heart tissues by studying them, such as how strongly the patches contract when stimulated by electricity.

Columbia researchers say they’ve invented something much better. Using heart cells from a baby rat, they’ve created in the lab tiny, three-dimensional hearts, each consisting of a single chamber. These hearts, less than one centimeter in diameter, can pump continuously for up to four weeks in test tubes filled with liquid nutrients. Each heart is connected to a tube through which it sucks liquid in and out of a reservoir; scientists monitor how strongly each heart pumps by adding or subtracting liquid from the reservoir, thereby altering the chamber pressure.

“The big advantage is that now we can examine the relationship between a heart’s size and its contractile strength,” says lead researcher Kevin Costa, a Columbia associate professor of biomedical engineering. “When a person suffers heart failure, his heart usually enlarges and changes shape. By controlling independently for heart size and strength, and observing how one affects the other, we’ll learn a lot about heart function.”

This kind of information could help physicians determine whether they should operate on a heart-attack victim to fix the size and geometry of his heart or give him drugs to increase the contractility of the heart cells, says Costa. He developed the miniature heart with Eun-Jung Lee ’07SEAS, who earned her PhD in biomedical engineering at Columbia last year.
Costa can induce heart attacks in the miniature organs, too, by touching them with a piece of frozen metal. This damages one section of the heart, mimicking the localized cell death that occurs when a clogged artery blocks nutrients from entering one heart chamber. “Is there anything we can do to help this injured region of the heart heal so that it starts contracting again?” asks Costa. “We don’t know yet, but that would be a real silver bullet.”


  Kenneth Eward / Photo Researchers, Inc.
  Columbia chemist Brent Stockwell can make the mutant protein Ras oncogene, depicted above, destroy the same cancer cells that it creates.

Cell out

Brent Stockwell made headlines last year by discovering a previously unknown type of cell death. He found that substances that react with oxygen, such as rusting iron, can accumulate in a cell to the point where oxidation tears the cell apart. “It’s a pretty violent process,” says Stockwell, a Columbia associate professor of biological sciences and chemistry. “The cell becomes overwhelmed in a sea of hydrogen peroxide, essentially bleaching itself to death. It completely disintegrates within a few hours.”

The story gets better: Stockwell recently discovered that cancer cells can be prompted to produce excessive iron, resulting in the self-destructive oxidation process. His research team screened 40,000 natural and manmade compounds and identified two, RSL3 and RSL5, that cause iron production in cancer cells to kick into overdrive. These two compounds are found naturally in plants and take on their lethal power only in the presence of a cancer-causing protein called Ras oncogene. Scientists have known for years about this dangerous mutant protein. But they had not yet found a compound that could kill it or, as Stockwell has done, trick the protein into destroying the same cancer cells that it spawns.
The findings appear in the March 24 issue of the journal Chemistry & Biology, in a paper coauthored with Columbia postdoctoral researcher Wan Seok Yang.

The discovery accomplishes a central goal of cancer research: to identify compounds that attack tumor cells without affecting healthy cells. Stockwell says the breakthrough could help scientists develop cancer drugs with fewer side effects than those that target all rapidly proliferating cells, including noncancerous cells whose destruction leads to hair loss and nausea.

“This information will help us discover new features of cancer-cell biology,” says Stockwell, who notes that the Ras oncogene is found in many, but not all, types of cancer cells. “The approach we’ve taken is general and can ultimately be applied to many different mutant genes and to many kinds of cancers.”