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Dr. Colwell's Remarks

 


"Using Remote Sensing in the Bay of Bengal to Predict Cholera Epidemics"

Dr. Rita R. Colwell
Director
National Science Foundation
Plenary Speech, Session on Challenging Frontiers in Biomedical Research
The 91st Indian Science Congress
Chandigarh, India

January 4, 2004

See also slide presentation.

If you're interested in reproducing any of the slides, please contact
The Office of Legislative and Public Affairs: (703) 292-8070.

Good afternoon, distinguished colleagues. I am honored by this opportunity to speak to you and I would like to thank Professor Datta and the Indian Science Congress Association for this invitation. My links to India go back many years. It is a pleasure to see many old friends here in India with whom I've collaborated.

We all know that science has become a complex global enterprise. In the late 1960s, when I started my research, science was conducted in individual laboratories and field sites. The sharing of data was relatively slow, and broad patterns could take years to discern. "Climate change" and "genomics" were not widely known terms, with the worldwide implications they have today.

Today, the study of environmental change, atmospheric forces, microbiology, and social science are inextricably linked, and the study takes place in real time and around the world. With satellites and supercomputers we monitor and model phenomena ranging from pollutants to marine populations to solar turbulence. We collaborate across disciplines and across national boundaries, often in virtual space.

New frontiers have opened in biomedical research, stretching from nanoscience to genomics, from epidemiology to ecology, and from mathematics to social science.

The connections between cholera--an ancient water-borne disease--and the environment illustrate the richness and reach of today's scientific activity. Full understanding of an infectious disease extends from countries to continents and beyond, and connects medicine to many disciplines across science and engineering. The scope of research spans the planet, connecting flora, fauna, earth, water, and sky. And with this broader perspective comes a responsibility to society to examine the full range of inputs and outcomes.

[Title slide ON: Using Remote Sensing]
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The title of my talk, "Using Remote Sensing in the Bay of Bengal to Predict Cholera Epidemics," previews the expanded framework in which many of us conduct our studies, whether in biomedicine, information science, nanoscience, or the emerging science of learning.

[slide not available]
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Before I begin the cholera scenario, I want to highlight three of the US-India research collaborations that are supported by the agency I direct, the National Science Foundation. These joint endeavors set the stage for a greater awareness of the interconnectedness of science. The current stage of cholera research continues the theme of science that spans continents and employs many viewpoints to unravel complex interactions.

US-INDIA RELATIONSHIP

[Hunting mushrooms in Narkanda]
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The more widely research and data are shared, the broader the perspectives that can be brought to bear on the findings. This leads to a fuller understanding, benefiting both the scientific community and society. For example, scientists from our respective nations, the United States and India, have teamed to study fungal distribution on two continents. Part of this study takes place in the Narkanda area, not far from here.1

Fungi are among the largest groups of living organisms and one of the most important to the functioning of ecosystems. Yet we know little about their populations and taxonomy. Using the tools of modern molecular biology, the scientists will assess and compare the genetic relatedness of species that are geographically far apart. This search for intercontinental patterns will provide insights into biodiversity's role in ecosystems and could lead to possible applications in forestry or agriculture.

[GONG solar observatories]
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Sciences far removed from biology, such as astronomy, also share the need for multinational perspectives. The Global Oscillation Network Group, or GONG, detects activity on the Sun by bouncing sound waves through its interior, much as seismologists do within the earth. The United States and India are among the five nations that host GONG solar observatories. However, at least 20 nations provide expertise, ranging from astrophysics to engineering to instrumentation and software. Knowledge about the evolution of the Sun and its relationship to Earth contributes to worldwide concepts about our origin and vulnerability and enhances our ability to predict solar storms that affect sophisticated man-made technology.

[slide not available]
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Another collaboration, in which US, Indian, and European scientists greatly advanced the frontiers of research, is the Indian Ocean Experiment, which uncloaked the Atmospheric Brown Cloud over southern Asia. This manmade aerosol haze is spreading from the Himalayan mountains to the Indian Ocean. The surprising scope of brown clouds, and the recognition that they are a common problem for many regions, calls for broad collaborations of scientists and nations to study the transport of pollutants around the earth. The complex link between clouds, chemistry, and climate requires interpretation from earth, ocean, and atmospheric scientists, as well as computer scientists and mathematicians. The US-India Center for Environmental Research is just one of the collaborations continuing this research.

Bringing complementary viewpoints to bear on global aspects of weather, climate, and pollution can speed our ability to predict storms, droughts, and anthropogenic haze and can help reduce the uncertainties in climate change science. This is an excellent example of how the scientific community and the public benefits from shared data analyzed from geographically different perspectives.

THE GLOBAL CONTEXT FOR HEALTH RESEARCH

[Cholera research crosses borders]
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Let me turn now to the study of cholera, which is framed by the same need for multiple perspectives. From a saltwater bay in Maryland, to microorganisms in the Indian Ocean, to rain in South America, my own research on cholera has surmounted national borders and the distinctions between disciplines. Our understanding of the disease's complex interactions with the web of life and the global environment could ultimately enhance our ability to predict its course.

[Frequent flyers]
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Health issues in the 21st century reflect the worldwide movement of people and goods and the recognition that earth processes operate on a global scale. International travel has skyrocketed in the past half century, up to almost 500 million international arrivals per year.

The study of disease must encompass the individual's relationship with the global environment. As Gro Harlem Brundtland—former director of the World Health Organization—has said, "In the modern world, bacteria and viruses travel almost as fast as money. With globalization, a single microbial sea washes all of humankind. There are no health sanctuaries."

THE BIOCOMPLEXITY CONTEXT

[Biocomplexity spiral]
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As the movement of living beings, whether invasive species or pathogens or humans, enlarges and encircles the globe, so does the scope of biological research. This image represents the conceptual framework I call biocomplexity. Biocomplexity is the study of the interactions between biological systems, including humans, and their physical environments.

Biocomplexity is a priority research area at the National Science Foundation and has long informed my own research on the interactions between climate and health.

We have learned that ecosystems do not respond linearly to change, nor do the pathogens that live in them. Here I use the form of a spiral, symbolic of life at every level, to underscore the point that understanding demands observations from multiple perspectives, from the nanoscale to the global.

The spiral of biocomplexity begins to unfurl at the scale of the atom, and curves up through successive levels of life, through the cell, the organism, the community, and the ecosystem. Disciplinary worlds, formerly perceived as discrete, intersect to provide fuller, more complex viewpoints.

The lens of biocomplexity helps us understand the links between climate and health. Infectious disease is a moving target—as climate shifts, any disease with an environmental vector will be affected.

[Climate Change and Human Health: WHO report]
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The World Health Organization, in a major report published issued last month on climate change and human health, attributes 2.4% of all cases of diarrhoeal diseases to climate change.2

As the report points out, the entire biosphere is our laboratory. As we recognize signals from climate models and incorporate them into public health measures, we learn how simplistic is the notion that we can successfully eradicate a disease from the face of the planet. With a global perspective, however, we begin to recognize opportunities for proactive approaches to prediction and prevention.

CHOLERA AND THE RELATIONSHIP OF CLIMATE AND HEALTH

[Global spread of cholera]
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Cholera's seeming links across continents led me and others to search for parallel patterns in disparate locations. Investigation of environmental factors, in particular, have provided a clearer picture of the disease, from virulence to transmission to epidemiology. With further examination of these links, we hope to move from understanding to prediction and, finally, to pathways of prevention.

[Biocomplexity spiral: molecular and organism]
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To understand the spiral of complexity that surrounds the mystery of cholera, we must begin with insights from the smallest scales.

Twelve of the 30 known species of the genus Vibrio produce toxins that can cause human disease. Cholera is caused by the pathogen Vibrio cholerae. But where did the pathogen come from? Its requirement for salt led us to suggest that its ancestral home is the sea, and recent advances in genomics have helped to substantiate this theory.

My students and I first discovered that the ocean is a reservoir for V. cholerae in the late 1960s, when we identified the organism in water samples from the Chesapeake Bay in the eastern United States.

[Tube worms and eel at undersea vent]
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Here is a community of life around a deep-sea hydrothermal vent. The isolation of the genus Vibrio from such vents was first reported in 1981.

[East Pacific Rise]
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In 1999, during dives by the submersibles Alvin and Nautile, sulfide chimneys were collected from hydrothermal vents on the East Pacific Rise, one of the fastest-spreading sections of the mid-ocean ridge. Vibrio species isolated from the chimneys bore molecular similarities to Vibrio cholerae, suggesting that it is native to the deep sea, and that it can survive in extreme environments.

[Vibrio cholerae: small and large chromosomes]
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In 2000, the genomes of the two chromosomes of V. cholerae were sequenced. The sequencing data confirm that V. cholerae is a versatile organism, able to live in several habitat types, in addition to the human gastrointestinal tract.

The 50 toxin genes reside on the large chromosome. A big break in the study of cholera came when Vibrio cholerae was found to have a gene acquisition system located on its small chromosome, allowing the lateral transfer of genetic material. Between the sixth and seventh pandemics, the organism acquired new DNA. A new strain has caused the deadly outbreaks of cholera in India and Bangladesh since 1992. A type of cholera that had previously not been known to cause epidemics had picked up toxin genes from other cholera in its environment.

This was a significant turning point in cholera research because we now knew a new strain could arise from genetic recombination and horizontal gene transfer. This underscores the versatility of cholera, and gives credence to our need to understand its capacity to evolve and adapt to its environment.

[Biocomplexity spiral: habitat and population]
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Moving up the biocomplexity spiral, we can trace the ecological interactions of V. cholerae populations in two distinct habitats: the aquatic environment and the human intestine.

[Copepod with egg case]
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In the aquatic environment, V. cholerae attach to live copepods, tiny zooplankton that thrive in the environment of the Chesapeake Bay as well as in the Bay of Bengal. The cholera bacterium has also been found in shellfish.

This copepod is a female whose egg case, on the left, is covered with vibrios. V. cholerae colonizes the oral region and egg sacs of copepods. As many as 7,100 vibrios have been measured on a single copepod. In an area where water is not treated, several copepods could be ingested in a single glass of water, containing an infectious dose that could cause cholera in a human being.

As populations of copepods fluctuate, so too does the presence of vibrios, a link being studied by one of my students. Our hypothesis is that cholera originally evolved commensally with marine animals such as copepods, which provided them a surface to grow, nutrition, and perhaps other mutual benefits.

The organism forms biofilms that enable it to adhere to copepods and shellfish. A molecular mechanism adapts these adhesive substances to the habitat of the human gut, helping the organism penetrate barriers and firmly attach.

[Sampling for cholera in Chesapeake Bay]
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In Chesapeake Bay, native V. cholerae populations fluctuate with the seasons, just as they do in South Asia. V. cholerae is more common in the portions of Chesapeake Bay with low salinity, and its population increases when the weather warms and freshwater influxes reduce salinity. In fact, temperature and salinity combined predict the presence of V. cholerae with an accuracy of between 75.5 and 88.5 %.

There is a similar relationship in the Bay of Bengal between the monsoons and cholera. With climate changes--carbon dioxide increasing in the atmosphere, global warming, and more rainfall--river flows could increase, lowering salinity and driving up V. cholerae populations even further.

Each new study provides a more cogent projection of what could occur. Two weeks ago, for example, oceanographers reported a link between climate change and changes in ocean salinity, finding evidence that the global water cycle is intensifying.3

[Biocomplexity spiral: ecosystem]
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Let's return to the spiral of complexity and examine cholera from the perspective of the ecosystem.

We discovered the correlation between changes in climate and incidences of cholera by analyzing satellite data on global ocean temperature and sea surface height.

[slide not available]
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We knew that cholera epidemics were seasonal. Using the remote sensing data, we discovered that cholera outbreaks in Bangladesh occur shortly after sea surface temperature and sea surface height reach their zenith. This usually occurs twice a year, in spring and fall.

Patterns in ocean temperature and height are also linked to the pattern of cholera outbreaks in South America. Simply stated, we have found a positive correlation between increased sea surface temperature and sea surface height and subsequent outbreaks of cholera.

Heating of surface waters, especially off a tropical or subtropical coast, results in an increase in phytoplankton. Through remote sensing, we can now determine when that bloom is occurring. The phytoplankton, in turn, provide food for zooplankton, including the copepods. The zooplankton increase, followed by an abundance of vibrios in the water.

[slide not available]
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Another potential influence on populations of V. cholerae in the ecosystem is the discharge of ship ballast. The scientist we see here is inside the ballast tank of a ship collecting water samples.

Cholera bacteria have been detected in the ballast water of ships entering the Chesapeake Bay and the US Great Lakes after an ocean crossing. It still has not been shown that cholera can colonize a new area this way. Nonetheless, if coastal environments warm, an organism adapted to warmer temperatures and transported in ballast water may be deposited in a new site and potentially cause a temporary, localized outbreak from ingestion of polluted shellfish.

Thus we see how factors at scales large and small, seasonal and microscopic, might interact to shape populations of infectious bacteria and provide clues to prediction.

[Woman straining water in Bangladesh]
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In cholera-endemic areas, human beings are part of the cholera bacteria's ecosystem. Yet there is a simple and inexpensive tool available to thwart its progress.

A sari cloth, available even in the poorest household, can be folded eight to ten times. This creates a less-than-20-micron mesh filter, as we determined by electron microscopy. We have found that straining water through several layers of sari cloth may be enough to prevent ingestion of infectious levels of cholera bacteria.

[Micrographs of old and new sari cloth]
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The pictures show why old sari cloth, not new, is preferred - because its holes are smaller (ca. 20 µ) and better able to trap plankton. Laboratory studies show that old sari cloth folded at least eight times provides an even smaller filter pore size, and can filter out more than 99% of the V. cholerae attached to plankton.

[Sari cloth filtration graph]
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We published in Proceedings of the National Academy of Sciences the results of a three-year study carried out in 65 villages in Matlab, Bangladesh, comprising a total study population of about 133,000 people. You can see the result here for filters made of sari cloth and nylon net versus the control group.

The incidence of cholera was reduced more than 50% in villages that used sari filters. The severity of disease also appears to have been reduced in villages that filtered, but this will need confirmation, which we hope to achieve in continuing studies.

[Biocomplexity spiral: planetary]
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Finally, we acknowledge biocomplexity from a planetary perspective. We return to the relationship between climate and health as we examine the largest epidemic of cholera to strike in recent years.

[Sampling for cholera on the coast of Peru]
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Cholera struck the coast of Peru in 1991, after nearly a century of absence from the Americas. Cholera has recurred in Peru following a seasonal pattern, with the greatest number of cases in the summer in cities along the coast.

[slide not available]
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Thousands of miles from the Chesapeake Bay and the Bay of Bengal, the pattern we had discovered held true. Studies of v. cholerae in coastal Peru found a correlation between increases in water temperature and the annual outbreaks of cholera, as well as a suspected correlation with the El Nino of 1990-1992.

We were able to carry out studies investigating this association, taking advantage of the predicted El Nino event of 1997-1998. Warm water along the coast, coupled with plankton blooms fostered by El Nino rains, appear to have helped amplify the population of cholera bacteria already in the environment. Because we were able to do field sampling prior to the 1997-1998 El Nino and to continue the studies during and after that event, we were able to link the cholera increase with the El Nino. The lines here show sea surface temperature, while the bars show rates of cholera.

Interestingly, both El Nino events and cholera outbreaks have increased since the 1970s, in Peruvian waters and in the Bay of Bengal. The climate-cholera link seen in the year of El Nino in Peru suggests yet another early warning system for cholera. My colleagues and I intend to give this further study. Once again, remote sensing of sea surface temperature and height, as well as plankton blooms, may play a role in prediction.

CONCLUSION

[Biocomplexity spiral with selected images]
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Thus the spiral of biocomplexity comes full circle, connecting climate patterns to the vicissitudes of cholera on three continents. Now we are poised on the threshold of prediction.

There is more work to be done. Satellite data suggest that certain temperature patterns unfold in the Himalayas six months before the incidence of cholera rises along the South Asian coast--a research direction on the cusp of being explored. An integrated earth observation system, a concept being discussed among several nations, would undoubtedly lead to additional research avenues.

With the wealth of new data on biology, health, and climate, we want to incorporate climate patterns into an early warning system for cholera. Only now is this becoming feasible, with the growth of technology to monitor, model, and communicate. As we navigate the tangled interactions between life and the environment, between climate and health, we advance our understanding and move closer to prediction.

Connecting cholera to climate exemplifies the complexity of today's science, requiring insights from international teams of physicians, microbiologists, epidemiologists, statisticians, ecologists, remote sensing scientists, and sociologists.

Mohandas Gandhi [Mahatma] once said, "In nature there is fundamental unity running through all the diversity we see about us." As we examine the vagaries of climate, microorganisms, and societies, we find the unity through science. The questions cross continents and disciplines, but still they intertwine. So, too, must the answers, between our two nations and among all nations.


1 Narkanda is approximately 180 kilometers northeast of Chandigarh, beyond Shimla. The fungi project involves Dr. Steven L. Stephenson, University of Arkansas; Jean-Marc Moncalvo, Duke University; and collaborators at Garhwal University and Himachal Pradesh Agriculture University in India.
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2 Climate change and human health - risks and responses, by A.J. McMichael, D.H. Campbell-Lendrum, C.F. Corvalán, K.L. Ebi, A. Githeko, J.D. Scheraga and A. Woodward, published in book form by World Health Organization, 2003, and announced December 11, 2003.
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3 "A change in the freshwater balance of the Atlantic Ocean over the past four decades," by Ruth Curry of Woods Hole Oceanographic Institution et al, Nature 426, 826-829, December 18, 2003, reports that saltier tropical oceans and fresher ocean water near the poles are signs of climate change's impacts.
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