A Protozoan Makes Bid To Move Into The Scientific Mainstream

TUCSON, Ariz.--Seven years ago, Charles Sterling came to the University of Arizona determined to find a new line of research. At the time Sterling, who was an expert in malaria from Wayne State University in Detroit, had grown tired of what he called the "nasty" world of big-time malaria research funding, a world rife with political infighting and fierce competition among scientists. So, at Arizona, he turned his attention to an obscure, little-studied relative of the malaria parasite, a protozoan called Cryptosporidium, and settled in. But not for long. As chance would have it, Sterling had stumbled into another research whirlwind when he discovered that Cryptosporidia were a much larger health hazard than anyone had imagined. In fact, thanks in part to a new diagnostic test that Sterling developed, the protozoan is being discovered in AIDS patients and in water supplies around the world. TUCSON, Ariz.--When tap water turns out to be less healthful than once thought, scientists aren't the only ones who notice. At one time, Cryptosporidium, a water-borne parasite that causes diarrhea, was not considered to be a problem in public water supplies. Now public health officials aren't so sure it can be ignored. A new diagnostic test has found that this pathogen is quite common. In one survey, it showed up in 77 of 107 water samples taken in six Western states. As a result, debates about Cryptosporidium have moved from the laboratory to the agendas of public health officials and funding agencies, where the organism is posing tough policy and financial questions. Consider New York City, where, with current technology, ridding the water supply of this organism could cost billions of dollars. But before taking such a costly step, experts must determine whether standard methods for water purification can purge the microbe from drinking water. And they must decide just how big a health threat it is and, consequently, how much money should be spent to protect people from exposure to it. So far this protozoan has eluded most public health detectives. There are many unexplained outbreaks of diarrhea where Cryptosporidia may have gone undetected. Between 1971 and 1985, the Centers for Disease Control in Atlanta and the Environmental Protection Agency identified the responsible organism in only about half of 502 water-borne outbreaks of diarrhea affecting 111,228 people. Another factor keeping Cryptosporidium from making headlines that might, in turn, generate research funding is the fact that healthy individuals recover from cryptosporidiosis without treatment. Charles Sterling, a parasitologist at the University of Arizona in Tucson, has developed a test to detect this parasite, which is excreted with the feces of infected hosts. But while Sterling's monoclonal and other detection methods recognize the protective casing, the oocyst, they are blind to reading the infective sporozoite inside. So it is impossible to tell whether the Cryptosporidium detected is capable of causing disease or is an empty or dead casing. The Cryptosporidium oocyst has shown very high resistance to practical levels of chlorine, ozone, and other widely used disinfectants, Sterling says, and it is not known whether those oocysts are still viable, that is, whether the sporozoite is still capable of causing infection. Filtration seems to be the only way to clear out the parasite, but it won't help the estimated 50 million people in the United States who drink unfiltered water. Some public water supplies are filtered, but many wells and large reservoirs are not. One potentially profitable solution is an effective agent for water treatment for Cryptosporidia. "If a company could show, `Well, look, my stuff does inactivate it, and it's fairly cheap to use,' " says Joan Rose, a parasitologist at the University of South Florida, "the EPA would say, `Well, okay, this is what you all will have to use.' And you've got the whole water industry to supply. So it could be very big bucks." Rose is discussing the testing of such a disinfectant with a company, which she declines to identify. A second solution is a better testing method. Right now, utilities that have Cryptosporidia in their watersheds face the prospect of having to pay for filtration, even though there now is no sure method of determining the viability of oocysts. The American Water Works Association Research Foundation recently gave Sterling $170,000 to develop a viability test. Also, Cincinnati's EPA branch that focuses on monitoring awarded Rose $200,000 over two years to develop a gene probe for Cryptosporidia, a step toward giving water utilities an efficient and affordable tool to detect the parasite in their sources. Such a tool also would come closer to clearly identifying viable and nonviable oocysts. Among the cities that depend on unfiltered water is New York City, which gets 90 percent of its 1.5 billion gallons each day from its Cat-skill/Delaware watershed. While that region is relatively protected, the city derives its remaining supply from its Croton-on-Hudson watershed, which includes runoff from developed areas. It plans to build a $600 million plant to treat the Croton water with ozonation and diatomaceous earth filtration. Charlotte Dery, water-quality manager for the Jerome Park Demonstration Water Treatment Plant, a prototype of New York's new plant, says she is confident based on surveys of its watersheds that the scarcity of Cryptosporidia in the Catskill/Delaware supply will help New York City meet an exemption and avoid having to filter that source. Otherwise, the Big Apple will have a big bill to pay. "If we have to filter for Cryptosporidium, it will cost New York City $4 billion," she says. --M.H.T. So once again, Sterling reluctantly finds himself drawn into the politics of scraping together research funding for a major threat to human health. The story of his and his fellow scientists' frustrations in this arena--as well as his recent success in landing $1 million to support his work--could help any scientist who is aiming to turn a quiet scientific backwater into a more visible and vigorous research endeavor. Or, in his case, one who wanders unwittingly into a hot research area. "We got in it at the right time," says Sterling, acknowledging that serendipity as well as foresight plays a role in science funding. "I'm happy that I got my funding. But what about all the other people out there that have brilliant ideas that should be funded?" They could begin, as Sterling did, by figuring out how to convince the biomedical establishment to train its financial guns on the tiny microbe. Sterling has made progress in doing so, but still has a long way to go. Although he has established the protozoan as a major health threat, cryptosporidiosis barely registers on a list of parasitic diseases being investigated. Fewer than two dozen academicians are researching this microbe. Most of them depend on the National Institutes of Health for support. But NIH officials seem preoccupied with understanding the HIV virus and have not diverted resources to long-shot studies of Cryptosporidium. In 1989, for example, the National Institute of Allergy and Infectious Diseases (NIAID) spent just $680,000 for Cryptosporidium studies; two-thirds of their projects were AIDS-related. And, until recently, the Centers for Disease Control in Atlanta ignored Cryptosporidium's role in AIDS infections. Drug companies, too, until recently, have shown little interest. But that indifference didn't deter Sterling. At first he used state and local resources to develop a monoclonal antibody diagnostic, now marketed by Meridian Diagnostics of Cincinnati, to detect the parasite. With this test, Sterling and others confirmed that Cryptosporidia weren't rare. In one 1986 study of water in six Western states, 77 out of 107 samples were contaminated. A study by American Water Systems, which operates about 100 private utilities, found evidence of the protozoan in 63 water supplies across the Midwest and New England. Sterling's suspicions had been fueled by reports in the medical literature of Cryptosporidium infections producing a cholera-like disease in AIDS patients. There were also large outbreaks in 1984 and in 1987 of cryptosporidiosis traced to tainted urban water supplies in communities in Texas and Georgia. In addition, recent surveys had found that this microbe may cause much of the diarrhea in Third World infants. So far, Sterling has prospered in this field, having managed to get support for his research. But he's an exception among his colleagues, who are finding that federal support is hard to come by. One reason for this low profile is that scientists have been unable to develop the animal and cell-culture models needed to apply sophisticated molecular biology techniques to examine the pathogen. As a result, problems with existing models weaken proposals in the eyes of peer reviewers, says biochemist Margaret Johnston, chief of the developmental therapeutics branch for the AIDS division at NIAID. That problem has led NIH to end its support for cell-culture work by at least one prominent researcher in the field. Rosemary Soave, associate professor of medicine and public health at the New York Hospital/Cornell Medical Center, says that NIH criticism that she has made insufficient progress in understanding the protozoan is, in part, justified. But she feels reviewers don't appreciate how hard it is to work with the organism. Reviewers insist on molecular probes to detect and track the microbe, she says, when the science is still too primitive to allow use of such techniques. "I spend days collecting stool and extracting the organism with Clorox to get enough to work with," she explains. "[The criticism] tells me that they have no feel for this at all." Progress has also been slowed by the tendency to give virologists, who wage war on HIV itself, priority when research funds are allocated. That inclination was fed, in part, by an early definition of AIDS that recorded only a patient's first opportunistic infection--infection that arises because the immune system has already been compromised by a primary infection. Such a definition underrepresented the numbers of those with cryptosporidiosis, which tends to develop later in the disease. That's no longer the case, however. While early studies reported that cryptosporidiosis affects fewer than one in 20 people with AIDS, recent studies that track all opportunistic infections, even those that develop late, show that it may infect nearly one in five. Even so, scientists studying these second-order pathogens in the AIDS epidemic are hardly awash in funds. "Our problems are no different than the people who are studying pneumocystis pneumonia, the number one OI [opportunistic infection] pathogen," said Kansas State University parasitologist Steve Upton. "They're having a heck of a time getting funding as well." But the federal government isn't the only funding source that has been slow to recognize the need to step up research in the field. Until recently the pharmaceutical industry has declined to embark on a quest for new drugs against the disease because of the limited market for scriptasporidiosis therapy. That attitude may be changing, however. More attention will probably be paid to this disease and other lesser opportunistic infections in the months to come because effective drugs against major opportunistic infections are already in the research pipeline, says NIH's Johnston. For example, Upjohn Co., American Cyanamid Co., Hoechst Celanese Inc., Mobay, and SmithKline Beecham have contributed drugs and expertise to Byron Blagburn, an Auburn University parasitologist seeking treatments for this infection. He also has $42,000 over three years from the American Foundation for AIDS Research to test chemotherapies with a mouse assay. Even the federal government is beginning to change its attitude. This year NIH earmarked $3 million out of a total of $600 million for AIDS research for studies of opportunistic infections. In 1991 Johnston expects to get at least another $2 million, and to double the number of grantees. Sterling is one of six grantees now in this program. In July, the NIH notified Sterling that his cooperative group, which includes University of Florida immunoparasitologist Michael Riggs, had won a $1 million grant for development of monoclonal-antibody therapy for scripta-sporidiosis -- a significant show of respect for the new microorganism on the block. Mark Holman Turner is a freelance science writer based in Tucson, Ariz.

A Protozoan Makes Bid To Move Into The Scientific Mainstream

Interested in reading more?

Become a Member of