At Radcliffe, microbiologist explains ‘biocomplexity’

The scientist who revolutionized the study of cholera paid a visit to Harvard this week.

On March 6, microbiologist and oceanographer Rita R. Colwell, a Johns Hopkins University public health researcher, delivered the last in a series of science talks in the 2006-2007 Dean’s Lecture series at the Radcliffe Institute for Advanced Study.

In three decades of research, Colwell has made major contributions to the understanding of cholera, an intestinal disease so ancient that its symptoms were first described in Sanskrit.

Colwell proved that the cholera germ, a bacterium called Vibrio cholerae, is a naturally occurring organism in the ocean, where it lives in zooplankton and survives seasonal cold cycles by becoming dormant. Colwell’s radical 1977 hypothesis defied the accepted dogma that cholera depended on the warm gut of humans to survive.

In the last few years, Colwell and her research team have pioneered the use of remote satellite imaging to track environmental factors that contribute to large-scale disease outbreaks.

In the case of cholera, the team uses climate-related factors such as water temperature, salinity, and ocean height to predict the threat of cholera, which in the spring and fall comes out of deep-sea dormancy to proliferate on mats of algae so vast they are visible from space.

Feeding on this phytoplankton are many trillions of copepods, one-eyed microscopic sea creatures related to shrimp and lobsters. They are the true reservoirs of cholera, carrying the germ around their mouths, in egg casings, and in their intestinal tracts.

Colwell said climate factors are still undervalued as predictors of disease. But they can be used to track the pathogens that cause not only cholera, but malaria, hantavirus, campylobacter, tularemia, and the yet-to-emerge avian flu.

Environmental factors like algae and water temperature, processed by computer systems capable of handling massive data, are powerful predictors of cholera. Colwell called this combination of data and method a new working model for tracking global disease. Her talk at the Radcliffe Gymnasium, before an audience of 100, was called “Oceans, Climate, Biodiversity, and Human Health: The Cholera Paradigm.”

Cholera, an acute intestinal disease marked by the sudden onset of severe diarrhea, still packs a mortal punch, killing about 10,000 people a year, and sickening 100,000 — mostly in undeveloped countries with marine coastal systems and no reliable sources of pure water.

The disease was once confined to South Asia, but in the early 19th century appeared in the West. A study mapping an 1854 cholera epidemic in London by physician John Snow traced the disease to a single infected water pump, and is considered the beginning of modern epidemiology.

Despite Snow’s example, the study of infectious disease is no longer a linear scientific pursuit of one cause for one effect, said Colwell. Instead, epidemiology has to “draw insight from a whole series of contexts,” from nanoscience and genomics to climatology, social science, geology, and mathematics.

Colwell is a theoretician of “biocomplexity,” a recognition that life is a spiral of interconnections ranging from the atomic to the cosmic. It’s a view that suggests that some problems can only be solved by combining and coordinating once-disparate branches of science.

The connection between cholera and the environment provides a good paradigm of how “a global context indisputably frames all of the human health issues in the 21st century,” she said.

The realities that make up that context include increased international travel and trade; the recognition that Earth’s environment operates on an interconnected global scale; and the reality of global warming (“unless you belong to the Flat Earth Society,” said Colwell), which will raise and warm oceans and shift disease vectors.

To keep up, scientific endeavor has to be on “the same global scale as the pathogens we target,” explained Colwell.

From the perspective of a “biocomplexity lens,” she said, it is evident that diseases like cholera are intimately linked in a chain of life forms, and will not be eradicated.

From that same perspective, “we also begin to understand infectious disease is a moving target,” said Colwell. “As the climate shifts, any disease with an environmental stage or vector is going to be affected.”

If signals from climate models are incorporated into tracking global disease, she said, “we have many new opportunities to be proactive rather than reactive in our approaches to public health.”

In one study, Colwell and a team of researchers designed a predictive model of cholera rates in a coastal area of Bangladesh using only environmental factors: sea surface height, temperature, and chlorophyll levels, as measured by remote satellites.

They chose a future date — June 14, 2004 — and using climate data from a few months before made an estimate of 24.3 cholera cases per 1,000. The actual rate of cholera cases on that day was 25.8 per 1,000 — proof of the power of environmental disease predictors.

The scheme also proves that understanding the “ecology of cholera,” noted Colwell, requires understanding the factors in their biocomplexity: global weather patterns, aquatic reservoirs like marine bays and estuaries, zooplankton and their surface-attached cells, biofilms, and the deep sea itself, the ancient home of Vibrio cholerae.

Environment aside, cholera could be prevented (as it is in the West) by the simple expedient of making clean water universally available. This will not happen easily or soon, said Colwell. To bridge the gap, her team came up with a low-tech answer in 1998 in Bangladesh: straining drinking water through sari cloth folded over at least four times. The native fabric creates a 20 micron-size filter, which strains out the zooplankton associated with cholera.

A pilot study in one Bangladesh village showed that this simple step reduced cholera cases by 50 percent in the fall of 2000.

Colwell was the first biologist — and the first woman — to be director of the National Science Foundation. She served from 1998 to 2004, and during her tenure more than doubled the agency’s budget and nearly doubled the size of a typical research grant.

At Radcliffe, Colwell called for an integration of global scientific paradigms to track and confront infectious disease. “We must protect this blue planet,” she said. “It’s the only one we’ve got.”