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Disease in humans and animals has been rising while human use of agricultural fertilizer has skyrocketed. A team of scientists led by researchers at the University of Colorado cites evidence that those two trends are related, but they say much is still unknown.

The relationship between “nutrient enrichment” and disease involves a “fair amount of smoke and a little bit of fire, though how much fire we don’t know yet,” says Alan R. Townsend, associate professor of ecology and evolutionary biology at CU.

He and his colleagues hope for more widespread research on this topic, which has large implications for human and ecosystem health.

Nutrient enrichment is both a boon and a bane. The advent of mineral fertilizer facilitated the Green Revolution, which began in the 1940s and greatly improved agricultural yield. But it also introduced vast amounts of reactive nitrogen and phosphorous into the environment.

Those nutrients have been linked with an array of human and animal diseases, notes a new study led by Pieter T.J. Johnson, CU assistant professor of ecology and evolutionary biology. The study was co-authored by fellow CU faculty Townsend and Valerie McKenzie, along with researchers from several other institutions and was published in the January edition of the journal Ecological Applications.

As Townsend notes, the incidence of disease is rising worldwide, and there is a potential contributor: “Global changes in nutrient cycles are the most rapid and most startling of any human change in the last hundred years … far greater than what we’ve done to the carbon cycle.”

“We’ve used more fertilizer in the last 20 years than in all of human history,” Townsend emphasizes. While there is a probable connection between nutrient enrichment and disease, he adds, “What you really want to know is what’s under the hood.”

McKenzie, a CU assistant professor of ecology and evolutionary biology, notes that relationship between disease and land-use changes is still a partly open question. But, “We’re highlighting the role of nutrients.”

Exposure to nitrogen compounds, such as nitrates in drinking water, can cause blue-baby syndrome, reproductive problems, and some forms of cancer. And while nutrient enrichment can improve human health and reduce malnutrition, human introduction of such nutrients “frequently correlate with increases in prevalence, severity or distribution of infectious diseases in nature,” the authors write.

While emphasizing how much remains to be studied, the scientists identify evidence that nutrient enrichment increases illness via three main avenues: by transmitting diseases directly, indirectly and through a complex series of interactions.

Coral reefs appear to suffer from increasing concentrations of nitrogen, for instance. Scientists have used time-release fertilizer pellets in controlled environments to gauge the effects of nutrient enrichment on corals that are already diseased. The extra nutrients doubled the severity of yellow band disease and black band disease, which kill coral tissue.

Malaria and West Nile virus are examples of diseases that can be indirectly influenced by nitrogen. In these cases, parasites carried by a “vector,” mosquitoes, infect human hosts.

Malaria kills about 2 million people annually, most of them children under 5, according to the World Health Organization. As the authors note, nutrient enrichment can increase the growth of larval mosquitoes.

Such a change in the system could give a reproductive advantage to one species of mosquito that, incidentally, more efficiently transmits the malaria parasite.

An instance of such a trend has been found in Belize, where phosphorus runoff has favored different and denser plant life, which has increased the abundance of a mosquito that is a more efficient carrier of the malaria parasite, the authors note.

Nutrient-rich environments can allow mosquitoes to breed more profusely. As McKenzie notes, the result is straightforward: “More vectors, more disease.”

Johnson has studied the complex transmission of disease due to nutrient enrichment. He found that aquatic environments with high levels of nitrogen and phosphorus, usually from fertilizer runoff or cattle grazing, precipitate a chain-reaction of parasitic infections in three species: birds, snails and amphibian larvae.

Johnson’s team was the first to report the mechanism of cascading events from excessive nutrient enrichment, or eutrophication. Freshwater snails become larger and more numerous with eutrophication.

According to Johnson, nitrogen and phosphorus from eutrophication promote algae growth, which increases the number and vigor of the herbivorous snails. Parasitic worms, called trematodes, infect these snails.

Those more robust and numerous snails harbor more trematodes, which in turn infect more frogs, he found.

Frogs infected with parasitic trematodes frequently suffer limb deformities, growing extra or malformed legs, Johnson found. Frogs with limb deformities are easier prey for birds, which eat the parasitically infected frogs and whose waste perpetuates the cycle.

While scientists have found evidence of all three types of nutrient-enhanced disease transmission, much more research needs to be done, Townsend notes.

Additionally, there is a link between nutrient enrichment and non-infectious diseases. Fertilizer runoff into rivers and coastal areas has been linked to “dead zones” in oceans, which damages marine life and the industries that depend on it.

Fertilizer runoff can also cause harmful algal blooms, in which algae and cyanobacteria spread rapidly, killing fish and contaminating seafood and drinking water, the authors note.

“It is important to note that the effects of nutrient enrichment vary among pathogens and do not always elicit higher disease risk; exacerbation of a broad suite of diseases does appear possible, but the decline or elimination of others is also possible,” the authors write.

The genesis of the Green Revolution is a century-old discovery that atmospheric N2 gas (which is inert) could be converted into reactive, biologically available forms of nitrogen. The rate of conversion from inert forms of nitrogen to reactive forms has increased 10 times faster than the rate of increase in atmospheric CO2, Townsend says.

The United States and European Union are the leading users of fertilizer, but developing countries in the tropics, which are striving to feed themselves as global population swells toward 9 billion, are rapidly increasing their use of nitrogen and phosphorous compounds.

“They all want to eat meat too,” Townsend observes.

McKenzie concurs, adding that by 2015 most of nitrogen impacts will be seen in the tropics.

And Townsend adds: “We’re going to be loading up the part of the world that is most disease rich and the part where people are the most impoverished.”

To that sobering observation, Townsend adds another: “As bad as climate change is, it’s at least possible to imagine a carbon-free future. It’s impossible with nutrients. You’ve got to have them. People have to eat.”

But the authors say there’s no need abandon hope, all ye who grow here.

The gloom-and-doom side of it is the scale and pace of change, Townsend says, adding: “That’s all spooky stuff. The silver lining to me is that I believe 100 percent that this is a problem we can fix.”

Reducing inefficiency is one opportunity. About 93 percent of fertilizer is wasted, Townsend notes. When fuel prices spiked recently, farmers sought ways to use fertilizer more efficiently, and such lessons could be extrapolated, Townsend suggests.

McKenzie, meanwhile, notes that the collaboration among three experts with different strengths advances scientific understanding and is one of CU’s strengths. Townsend is a biogeochemist, while McKenzie and Johnson study disease in overlapping but slightly different areas.

“CU is one of the best places I’ve ever been around for fostering interdisciplinary work in environmental science,” Townsend says. “Now that we’re facing these big complex challenges, that’s what you need to solve them.”

With CU’s cooperative institutes and collaborative culture, he adds, “It’s no accident that CU’s been one of the top universities for environmental science for two decades.”

And while emphasizing that much remains unknown, Townsend says, “Five to 10 years of focus on this will put us in a totally different position.”

“That’s the excitement of science, that there’s a lot of work to be done.”

The trio’s work is funded by the National Science Foundation, and Johnson is supported by a fellowship from the David and Lucille Packard Foundation.