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The Worm Hunters

Pitt researcher unites the Americas

Zooming up the Americas, the e-mail raced north, fired from a keyboard at the only university chemistry department in Uruguay.

A researcher from Montevideo was writing to see if Pitt could share its chemical know-how to help battle a cruel intestinal worm that was emaciating cows and sheep in that South American country. The researcher’s message wired its way to the 13th floor of the University of Pittsburgh’s Chevron Science Center.

The international e-mail caught the attention of Chemistry Professor Peter Wipf. He wrote back the next day. The researchers exchanged papers and publications. They applied for (and won) a $120,000 grant. They collaborated, North American to South American.

Five years later, Wipf and his team at Pitt have concocted nearly 60 chemical compounds and mailed them by the vialful to the Uruguayan chemist. She is testing the compounds’ parasite-fighting powers on laboratory rats injected with the worms—research that could lay the groundwork for discovering a treatment for cows and sheep with the malady.

Gloria Serra is thankful her electronic SOS to the world found a reader. "The collaboration between institutions of different countries is needed and helps each other to improve knowledge and research," Serra says from her office at the Universidad de la Republica in Montevideo, where she is assistant professor of chemistry. "In our case, the (grant) collaboration allows us to research without funding limitations and to discuss our results with Professor Peter Wipf, one of the most qualified scientists in our field."

Wipf, a 2002 American Association for the Advancement of Science Fellow, sees his mission as helping find a solution to the parasite problem while establishing ties across the Americas. He believes the Northern Hemisphere ignores tropical and Third World health problems at its peril.

"We shouldn’t forget we have a lot of common problems," says Wipf. Nobody in the United States cared about the West Nile Virus when it was in Egypt or Sudan.

"Today, nematodes [tropical intestinal worms] might not be a problem in America. Tomorrow, they might."

These nematodes are indeed nasty. Infected cows and sheep weaken and lose weight, so much so that milk, meat, and wool production drop significantly. These parasites rob agriculturally dependent Uruguay of about $40 million each year, according to Uruguay’s Ministry of Livestock, Agriculture, and Fisheries. Some experts estimate that nearly one out of every two sheep is infected, numbers that put Uruguay among the worst in the tropics. Dogs get the worms, too, and in Uruguay, nearly one out of three suffers from them.

There is no preventive vaccine. The stomachs of infected laboratory rats balloon to three times their normal size. The medicine available today is expensive and doesn’t kill all 50-to-100 varieties of parasites that can get into animals’ digestive systems. Worse, some worms are now starting to resist the treatments.

Unfortunately, an affordable, broad-spectrum treatment could be anywhere from 10 to 20 years away, Wipf says. Today, it costs upwards of $18,000 to manufacture a year’s supply of daily doses. Farmers in developing nations could never afford that—and that is medicine for just one animal. To be within reach for the Uruguayan farmer, the price needs to be more like $1 for a year’s supply, Wipf says.

"We know which compounds work well, but we don’t have small enough molecules to produce them cheaply. You can’t have sheep pay $10 per prescription," says Wipf.

A condition that ravages only the animals of tropical farmers isn’t the kind that makes pharmaceutical companies throw millions at researching a cure, either. That leaves scientists from plagued countries to carry out the slow, laborious work of testing new compounds for potency.

In many cases, those plagued countries don’t have the money to fight disease with research. In Uruguay’s case, Serra notes that the Uruguayan government’s investment in science and technology is miniscule: 0.2 percent of Uruguay’s gross domestic product. That is lower than Haiti’s investment in science, she says.

Uruguay is also overcoming years of military rule that dispersed many of its best scientists. The junta’s reign ended in 1985, and some scientists returned to lay the foundation for a prospering research environment—hence, Serra working at the nation’s only university chemistry department.

The country’s apparent disadvantages put Serra and Wipf in a good position to win the $120,000 grant from the John E. Fogarty International Center for Advanced Study in the Health Sciences. The center, an arm of the National Institutes of Health, supports scientific research and training internationally to reduce disparities in global health.

Toward this end, Wipf capped years of e-mailing Serra with an October visit to her laboratory in Montevideo. They discussed how to continue their project. He also taught classes three hours each day to Uruguayan students in subjects like cross-coupling reactions, metathesis reactions, heterocycles, peptide mimetics, and natural products synthesis—just to name a few.

That last topic is one of Wipf’s specialties as a chemist. Natural products synthesis means creating complex compounds from simple and inexpensive chemical building blocks. Serra originally contacted him in 1998 after reading a series of Pitt chemistry publications explaining the University’s work with two such building blocks, oxazoles and thiazoles, which show promise against intestinal worms.

The two products are commonly found in sea snails, marine sponges, and filter feeders. Pitt researchers developed methods to make them from amino acids and peptides—naturally occurring building blocks of proteins and enzymes. Owing to the easy availability and abundance of these precursors, Serra and Wipf can prepare several of the compounds and test them for their ability to cure laboratory animals of intestinal parasites.

These are brand-new, never-made-before chemical compounds, itching to prove themselves in a world of menacing disease. Perhaps therein lies the wonder of chemistry: It allows for endless new products, starting with simple and inexpensive building blocks and by making—and sometimes breaking—their chemical bonds in a laboratory.

It’s no stretch to say that chemists can invent the future in a flask. Part of that wonder is, no doubt, what inspires many chemists to get into the field in the first place.

"I bought a chemistry set when I was in fifth grade in Switzerland and had a lot of fun doing the experiments and working with the chemicals in the set," says Wipf, who grew up in Switzerland. "I also did not understand most of it, which challenged my curiosity."

Serra and Wipf's grant expires this spring. If the professors can get the grant renewed for another three years, their team can make thousands of new compounds for use in this battle, Wipf says.

While graduate and postdoctoral students mix new compounds in the Center for Chemical Methodologies and Library Development at Pitt, Wipf voices optimism about a future remedy to the difficult situation in Uruguay.

"I hope that international collaborations between research groups such as Gloria’s and mine will inspire governments in all countries to allocate resources to tackle human and animal health problems proactively instead of waiting for a remedy from the for-profit industry or the coincidence that someone might stumble upon a solution."
— Jonathan Szish

Breakthroughs in the Making

How long must a woman wonder whether she is pregnant" How many sweets will tempt a young boy who is waiting to find out if he is diabetic" It depends on how quickly the lab processes blood samples.

One day, people may not have to wait in prolonged agony for test results. Doctors will immediately inject the patients’ blood into a handheld device, which will analyze the sample. This day hasn’t arrived because of complications with the mixing and movement of fluids in microchannels (tubes the diameter of a strand of hair) within the device.

The work of Pitt Engineering Professor Anna Balazs and Research Associate Olga Kuksenok could remedy this by mathematically predicting the behavior of fluids flowing in microchannels. They are collaborating with researchers at the Oxford Centre for Advanced Materials and Composites, where Balazs was recently named a senior visiting fellow.

The pharmaceutical, food, and cosmetic industries already test formulations in microchannels to cut costs, labor, and experiment time when developing products. Balazs’ findings may spur the use of microchannels in several industries.

This three-year fellowship also allows Balazs and Research Associate Rolf Verberg to work with Oxford’s Department of Physics to find an optimal lubricant to push sliding surfaces, such as gears, apart and prevent them from abrading. Making gears last longer could cut down on repair costs for things like automobiles, washing machines, and elevators.
— Kelly Rottmund

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