Rita Colwell: Keeping Her Aim on Cholera

Photo of Rita Colwell

Dr. Rita Colwell. Her breakthrough finding in the 1960s that the microscopic Vibrio cholerae (V. cholerae) bacterium that causes cholera has a natural home in water still irks many in the medical community. Image Credit: Rita Colwell.

When cholera killed hundreds living in coastal towns and epidemics were linked with sea travel, newspaper cartoons at the turn of the century depicted the disease as a ferocious sea monster poised to attack fishermen resting on the docks. Today, the disease is still a scourge that claims hundreds of thousands of lives in developing countries every year.

Dr. Rita Colwell, the internationally acclaimed oceanographer and microbiologist, has spent the bulk of her career studying the microscopic Vibrio cholerae (V. cholerae) bacterium that causes cholera. She and her colleagues have found V. cholerae in oceans around the world, in isolated lakes and rivers untouched by fecal contamination, and even in volcanic springs in Iceland. Colwell and her team were the first to use remote satellite data to develop a predictive model for cholera outbreaks in east Asia, and she is the first scientist to link global warming with a potential rise in cases of infections disease. Most recently, Colwell and her team have applied genomic analysis to confirm that the heartiness of V. cholerae by showing the genome’s evolution through horizontal gene transfer.

It was in the 1960s when as a young researcher Colwell identified the V. cholerae bacterium in Maryland’s Chesapeake Bay. Colwell found that the bacterium attaches itself to the microscopic aquatic zooplankton and thrives in the copepod’s gut. Since then, Colwell and her team have reported that cholera’s growth is affected by salinity, weather, sea surface temperature and other environmental factors.

Yet it was the initial discovery in the Chesapeake Bay that changed the research world’s perception of cholera.

“This was a significant finding,” says Dr. Shafiqul Islam, professor and senior faculty fellow with Tufts University, who studies cholera in developing countries. “Dr. Colwell found that V. cholerae was living in the zooplankton, that it has a host in the environment. In this way she said that cholera can’t be eradicated.”

Colwell says she faced a great deal of resistance when she first published her research showing that the bacterium occurs naturally in the environment.

“I received very negative, in fact hostile reaction, on the part of the medical community because until then it had been considered transmitted only person-to-person. They had not been able to isolate it in between epidemics,” she says.

An electron microscope image of Vibrio cholera that has been negatively stained. Vibrio cholera is the bacteria responsible for the gastrointestinal disease cholera.

An electron microscope image of Vibrio cholera that has been negatively stained. Vibrio cholera is the bacteria responsible for the gastrointestinal disease cholera. Image Credit: Tom Kirn, Ron Taylor, Louisa Howard; Dartmouth Electron Microscope Facility.

Then in the 1980s, Colwell was able to show that the bacterium goes into a dormant phase, accounting for why it couldn’t be found between epidemics. “It is accepted now,” she says. “This research is in textbooks and more than 1,000 papers have been published” on the subject.

Today, controversy still surrounds the cause of the disease. Many in the medical community balk at Colwell’s research and maintain that drinking water polluted by sewage and fecal matter is the primary source of the diarrheal disease. Still, other researchers worry that funding for research designed to develop new vaccines might evaporate if scientists all agree that cholera can’t be eradicated.

“There seems to be a kind of mantra that cholera is caused by feces and sewage, and of course, person-to-person transmission is pretty powerful,” Colwell says. “But in studies we have done over the past 40 years, we have seen that there is no question that the cholera bacterium is in the environment. We have found the bacterium in the Chesapeake Bay, and we know that 100 years ago, there was an epidemic in Baltimore; Washington, D.C.; and New York, in Paris and in Italy. So the seed, so to speak, for the epidemic is in the environment.”

Cholera can be a fast acting diarrhea disease that causes severe dehydration and death if treatment is not prompt. Yet treatment is simple: Oral rehydration salts can cure up to 80 percent of people within a few days, Colwell says. But this treatment is elusive during an epidemic in countries that lack water treatment facilities. According to the World Health Organization (WHO), more than 1 billion people lack access to safe drinking water worldwide. Cholera is caused when people ingest food or water contaminated with V. cholerae. An estimated 3- 5 million people fall ill with this disease each year, and 100,000–120,000 people die. The bacterium’s short incubation period of two hours to five days enhances the potentially explosive pattern of outbreaks, WHO reports.

A world-class scientist

Colwell is one of the world’s top scientists known by many for her paradigm-shifting research on cholera. She is a distinguished university professor at the University of Maryland at College Park’s (UMD) Department of Cell Biology and Molecular Genetics, and at Johns Hopkins University Bloomberg School of Public Health. She also is the chairman of Canon U.S. Life Sciences Inc., a subsidiary of Canon U.S.A. that pioneers new applications in diagnostics and medical instrumentation, and sits on numerous boards and advisory panels. She has been active in the federal government: From 1998 to 2004, Colwell served as the 11th director of the National Science Foundation, an independent federal agency and the funding source for approximately 20 percent of all federally supported basic research conducted by America’s colleges and universities.

Dr. Anwar Huq, left, and Dr. Colwell in Bangladesh demonstrate how to filter drinking water using everyday sari cloth. Image Credit: Rita Colwell.

Dr. Anwar Huq, left, and Dr. Colwell in Bangladesh demonstrate how to filter drinking water using everyday sari cloth. After five years, the researchers found that as much of 48 percent of the V. cholerae was removed from the drinking water. Image Credit: Rita Colwell.

Her rise to the top of her field wasn’t always easy, Colwell says. In her senior year of college, Colwell says, one professor rejected her request for a fellowship, saying, “We don’t waste fellowships on women.” She eventually received funding from another advisor and completed a Masters degree in genetics, then a Ph.D. in Oceanography.

After publishing some 700 research papers on cholera, Colwell says that her most exciting new work is applying several genomic techniques to the V. cholerae involved in the Haitian epidemic. Cholera exploded there in the fall of 2010, 10 months after a magnitude-7.0 earthquake turned many of the country’s buildings and homes into rubble. Most Haitians didn’t have access to clean drinking water before the earthquake. So, when cholera hit, there was not enough clean water to treat the hundreds of people who fell ill in just a few weeks. The epidemic continues in Haiti: Nearly 470,000 people have been sickened and 7,000 have died as a result of the disease, according to the U.S. Centers for Disease Control.

Colwell and her team got to work trying to figure out what it was about the V. cholerae strain that caused so many people to die in Haiti. Working with UMD graduate students, Colwell examined stool samples from 81 Haitian patients with cholera symptoms that had been collected by a physician very early in the cholera outbreak.

After using multiple genomic techniques, Colwell found that two distinct V. cholerae serotypes, or populations, contributed to the Haitian cholera outbreak. One population resembled a strain found in South Asia and Africa. The second population resembled V. cholerae found in the Western hemisphere, which suggests that this population could be indigenous.

In another research paper published in 2009 in Proceedings of the National Academy of Sciences (PNAS), Colwell and colleagues demonstrate that as much as 40 percent of the V. cholerae gene can be transferred from one strain to another. “We were able to show that V. cholerae undergoes genetic shift and genetic drift,” Colwell says. This short-term and long-term genetic drift and shift highlights that the bacterium are versatile, and evolve often in response to environmental conditions, she adds.

Colwell’s findings complicate matters for those trying to pinpoint why the Haitians are in the grip of a cholera epidemic for the first time in at least 50 years. A report from the United Nations Independent Panel of Experts on the 2010 outbreak concluded that this epidemic is the result of water contaminated with fecal matter contributed by U.N. peacekeepers, originally from Nepal, who came to help the Haitians manage during the aftermath of the earthquake.

Colwell says she isn’t interested in blaming anyone for Haiti’s epidemic. “Our research shows that the cause of the epidemic in Haiti is complicated,” Colwell notes. The situation in the tiny country was primed for a cholera outbreak, she says. The earthquake washed silt and limestone into the river system, creating alkaline conditions that cholera vibrios thrive in at the same time the country experienced an extremely hot summer. The disaster also devastated the country’s water and sanitation systems. “All of these factors favored the spread of V. cholerae and led to the disease epidemic,” she says.

Helping to control the disease

In tropical East Asian countries, cholera is most active in April and May, and then again in September and October. With this regularity, would it be possible to predict cholera outbreaks? Colwell was eager to find out. In a 2008 research paper published in PNAS, Colwell and a team of international researchers sought to identify the environmental signatures that were associated with cholera epidemics in Kolkata and in Matlab, India. The researchers used different remote satellite-derived data for chlorophyll (CHL), sea surface temperature (SST) and local rainfall collected during a nine-year period, September 1997–December 2006, for which all three environmental datasets were available.

This figure shows chlorophyll in autumn over the Bay of Bengal region. Image Credit: Dr. Antarpreet Jutla.

This figure shows chlorophyll in autumn over the Bay of Bengal region. Image Credit: Dr. Antarpreet Jutla.

“The fit was uncannily good,” Colwell says about the link between CHL, SST, and patient cases of cholera. Although an operable real-world predictive tool is still a few years away, its usefulness can’t be emphasized enough, she says. The goal is to prepare pubic health workers, “so they can move in more quickly to boil water and put in place different filtration devices in the race to control the disease so you don’t have it spreading,” Colwell says.

A Tufts research group led by Islam, the Tufts professor, applied Colwell’s initial findings to relate chlorophyll levels and cholera outbreaks in the Bay of Bengal. Islam and colleagues used satellite data from NASA to measure the density of chlorophyll and track the blooming of phytoplankton, which is food for the zooplankton copepod.

The Tufts team is working on a satellite-based model to predict potential cholera outbreaks at least three to six months in advance, Islam says. The model has been developed and tested with chlorophyll information from satellites over the Bay of Bengal region to predict cholera outbreaks in Bangladesh. The team is currently working on testing the model with ground-based observations, he adds.

A link with climate change

Colwell’s research also illustrated that warm waters encourage the vibrio’s growth, and she was the first scientist to link climate change and climatic events, such as El Niño, to a possible increase in cholera cases in developing countries. Along with Carla Pruzzo of the University of Genoa, Colwell recently published a study with data spanning 40 years showing that as the temperatures increase in the oceans the number of vibrios has gone up.

“I would say there is a link that leads to a risk,” Colwell says about the connection between warmer temperatures caused by climate change and increased water-borne diseases. “I think the Haitian situation shows what happens when you’ve got very poor sanitation, severely disrupted communities, weather conditions all primed for a massive cholera epidemic.” The situation is less dire for industrialized countries with water treatment systems in place. “If severe weather conditions lead to a breakdown in the delivery of safe water, people in industrialized counties also will run the risk of enteric disease that come with unsafe water,” Colwell says.

Preventing the spread of cholera doesn’t always require high technology. In 1999, Colwell and her colleague Dr. Anwar Huq of UMD used simple cotton sari cloth as a filter for drinking water in Bangladesh. A total of 150 Bangladeshi women in 15 villages poured their drinking water through folded sari cloth and reduced the presence of V. cholerae by 48 percent. Five years later, the researchers returned to find that the women were still filtering their water with sari cloth. The researchers reported in published research that the filtration technique had spread to other villages once people there learned of it.

After years of studying V. cholerae, Colwell says her message is a simple one: “If you provide safer drinking water, it does a tremendous job of preventing the spread of disease.”