Paul Mittermiller

Taking Aim Percy Nuñez uses a slingshot to knock down and collect small branches that are too high to reach.

EVEN AS THE BUS zips along the Ecuadorian highway, botanist Percy Nuñez' eagle eye has spotted by the roadside two of the plants his fellow travelers are hunting. He yells for the bus to stop. He hops off, clips stems and leaves from the plants, and hands them to Michael Vishnevetsky and Marina Santiago. Santiago gives a loud "woo-hoo," raising her arms in triumph.

Vishnevetsky and Santiago are two of the 16 students in the undergraduate course Rainforest Expedition & Laboratory taught by Yale University professor Scott A. Strobel. The class has spent half of the semester preparing for this adventure in March, which I joined. They are hunting endophytes—fungi and bacteria that live inside plants. These endophytes often produce chemicals that ward off other microorganisms, thereby securing a particular plant for themselves. The endophytes may also produce chemicals that help their host plant and may even contribute to long-known medicinal effects of plants.

Strobel, a professor and chair of the molecular biophysics and biochemistry (MBB) department at Yale, received the $1 million grant that funds the rain forest class when he became a Howard Hughes Medical Institute Professor in 2006. The HHMI Professors program aims to bring research to the undergraduate curriculum by giving research professors the money they need to innovate in the educational realm the way they do in their research.

Strobel started thinking about the class after a lunchtime conversation with William Segraves, the associate dean for science education at Yale. Segraves told Strobel that HHMI was soliciting proposals for HHMI Professors and asked Strobel to consider being a nominee.

As Strobel walked back from lunch, contemplating what might make a good proposal, he thought about his dad's research. Gary A. Strobel, a professor of plant sciences and pathology at Montana State University, has combed many of the world's forests and jungles, looking for plants that harbor endophytes and the compounds those endophytes produce. Gary Strobel has successfully collaborated with undergraduates on such projects.

"The first thought I had," Scott Strobel says, "was what if he went out and collected stuff that we brought to Yale and used to isolate microbes." As he walked another block, he realized that the size of the grants made bigger dreams possible. "It's a quarter of a million dollars a year, and the science lab part isn't that expensive. Why don't we just take the students to the places my dad goes and then do the endophyte isolation in the summer?"

Gary Strobel accompanies his son and the students on their travels and visits them during the summer, helping guide the collection and lab work. The older Strobel is easy to spot on the trail, wearing his signature red knit cap that unfurls to the size of a windsock to become a sampling bag. During the academic year, students who continue their research seek his advice via telephone and e-mail.

Gary Strobel also forged the connection with Nuñez, an Incan botanist at the National University of San Antonio Abad, in Cuzco, Peru. With Nuñez' vast knowledge of the native flora, the expedition is far more successful than it would have been otherwise.

Before receiving the grant, Scott Strobel spent nearly 10 years as the coordinator for undergraduate education in Yale's MBB department. In that role, he oversaw the research-for-credit portion of the major. He noticed that successful students use the first person personal pronoun when they describe their work—my project, my idea, my experiment.

Celia Arnaud/C&EN

In The Cards Vishnevetsky (left) and Salvador Nuñez (right) consult with Percy Nuñez.

"It sounds selfish, but it really indicates that they've taken possession in a concrete intellectual way of what they're thinking about and what they're doing," he says.

In contrast, struggling students talk about experiments and ideas belonging to other individuals such as postdocs or professors, the younger Strobel notes. "It's clear they haven't taken possession," he says. "One of the key things I wanted to figure out was how you give them control."

GIVING THE STUDENTS ownership of their research is a driving force in the rain forest class, and that ownership starts before students collect their first plant, with each student selecting a theme for his or her collection. Most of the students choose medical applications, including women's health issues or treatments for various diseases. Choosing their own topics increases the students' commitment to the research.

The students did their homework preparing for the trip, using ethnobotany resources to compile their lists of desired plants. Some of the plants grow in the high-altitude cloud forest. Other plants flourish in the Amazonian rain forest. Still others thrive in the dry forest.

The students prepared 8.5- x 11- inch crib sheets with photos and other information about their plants. To protect against the damp environment, the students waterproof their cards. Some students think ahead and laminate their cards back at Yale. Other students wait until they get to Ecuador to slip the sheets into plastic sleeves closed with duct tape.

On collecting days, the class splits up and troops into the forest, students carrying their cards along with clippers, plastic bags, global positioning systems, and two-way radios. The forest is abuzz with the sounds of wildlife—sometimes birds, sometimes monkeys—chattering in the forest canopy. As the students slog along muddy trails cut through the dense green vegetation, they keep their cards handy, scanning their surroundings for the real-life matches of the photos. They show their cards and describe their themes to anyone who might be able to help them. Such requests pay off when the guides who accompany the group direct the students to potentially useful plants that aren't on the lists. The airwaves crackle with the sound of students calling each other on the walkie-talkies to say, "I found your plant." Occasionally, student Salvador Nuñez (no relation to Percy Nuñez) lets loose a Tarzan yell.

Michael Marsland/Yale University

Artful Lab Kassie Dantzler works in Scott Strobel's lab, which is decorated with a rain forest mural.

Many evenings in the lodges and hotels are dedicated to preparing samples from the plant clippings. The fastest way for the students to identify their plants is to ask Percy Nuñez. Many of the plants he recognizes on sight, but for others, he consults a taxonomic guide.

On the first night, the group takes over the dining hall at their lodgings in the cloud forest. They haven't worked out a scheduling system yet, so the students jockey for position to see Percy Nuñez. The line snakes between the tables as the students await their turns with the botanist and his book.

Once they confirm the identity of their specimens, the students press two herbarium samples from each plant—one each for the botanical collections at Yale and the Ecuadorian Museum of Natural Sciences. The students also prepare two small stem samples they will work with when they return to Yale.

After two weeks of collecting and preparing plant samples in Ecuador, it's time to head home. Upon their return to Yale, the students plunge into the lab portion of the class. First, they need to culture the fungi lurking within the many plants they brought back. They place a small piece of the woody stem on a petri dish and wait to see what microorganisms poke their way out of the stem. The students then transfer spots to new plates until they have pure cultures with only a single fungus on each plate.

The students assay their endophytes against a number of disease-causing microorganisms, such as the bacterium Staphylococcus aureus and the yeast Candida albicans. This battery of assays helps them narrow their focus to the more biologically active fungi.

The students then screen endophytes that pass those tests in bioassays specific to their individual interests. This year, Scott Strobel required each student to find another professor on campus who could suggest an assay that would screen compounds for properties related to that student's theme.

Celia Arnaud/C&EN

Hopeful Harvest Santiago clips plants in the cloud forest.

"The simpler the assay, the better," Strobel says. "But it has to be from a faculty at Yale, and it has to be reasonably high throughput, meaning you could take 100 or 200 samples and assay them." In most cases, the students screen all the extracts collected by their classmates, not just their own.

In the summer after the trip to Ecuador, the class takes over a teaching lab. Students who continue their research during the following school year move to the "rain forest lab" that Strobel carved out of his own research lab to give the students their own space. The lab, decorated with a bright rain forest mural, is too small for the entire class but allows three or four students to work at a time.

The class has been a life-changing experience for some of the students. Sun J. Lee, a senior majoring in molecular biophysics and biochemistry, enrolled in the class the first time it was offered, in spring 2007. As one of Yale's Beckman Scholars—who are funded by the Arnold & Mabel Beckman Foundation for two summers and an academic year of research—she used the academic-year portion of her stipend to return to the rain forest with the 2008 class and collect more plants for her research project.

LEE SCREENS extracts from endophytic fungi to find compounds that can help prevent preterm birth. She works with Irina Buhimschi, an associate professor in the obstetrics, gynecology, and reproductive sciences department at the Yale School of Medicine.

Lee's experiments involve treating biological material discarded after delivery—placentas and fetal membranes—to find fungal extracts that inhibit inflammation. These experiments may lead to the discovery of new ways to prevent preterm birth and the brain injury that is often seen when babies are born too soon. Lee has found a hit and is continuing to identify and characterize the active components. By early this summer, she had identified at least one active component. She will be presenting the results of this research at the Society for Maternal-Fetal Medicine annual meeting in January 2009.

When Lee was deciding how to proceed with the fungal extracts, she sought a mentor who could guide research in reproductive science. She sent a barrage of e-mail messages to professors in departments throughout the medical school and made contact with Catalin Buhimschi, who suggested that Lee should actually talk to Irina, his wife and scientific collaborator.

Lee has long known that she wants to go to graduate school, and her experience with the rain forest class and the long-term research project it has catalyzed are further shaping her goals. She now plans to pursue a dual M.D./Ph.D. degree.

"Before I started" in Irina Buhimschi's lab, "I was so unsure if I wanted to do this dual degree," Lee says. She considered just sticking with the basic sciences, as many of her professors encouraged her to do, but she felt frustrated by pure science. "Where am I connecting to real people?" she recalls thinking. "Then I came here and was doing such relevant research. People say that being a physician and a scientist is hard, but I've seen people do it. I know it's possible."

The class played a major role in convincing another student to attend Yale in the first place. Blair Benham-Pyle had been accepted by Yale but had not yet decided to attend.

While searching the Yale science website for professors to visit during "Bulldog Days," an annual event held after students receive their admission offers but before they must accept or decline, Benham-Pyle saw an announcement describing the class.

"I thought this is seriously cool. I e-mailed Scott Strobel, and he responded within 24 hours," Benham-Pyle says. "We met during Bulldog Days and talked for 40 minutes. I got so psyched about the class that it's one of the reasons I ended up going to Yale."

Courtesy of Scott Strobel

Fearless Leader Scott Strobel wades into muddy waters.

IN ADDITION to helping her choose her undergraduate university, the class may help her decide what to do when she graduates.

Benham-Pyle, now a junior MBB major, is interested in science policy. When I chatted with her during the two-hour boat trip up the Napo River to the rain forest, she thought law school was the right path toward that career goal. Her success in the lab has convinced her that research might be a better option instead. "There's more than one way to reach that goal," she says.

Like Lee, Benham-Pyle is one of Yale's Beckman Scholars. Benham-Pyle attributes the success of rain forest students in winning this honor to the research focus of the class. Each student has his or her own project that makes writing a strong proposal easier, Benham-Pyle says.

Benham-Pyle is continuing her research project even after the class has ended. She is already close to identifying an active compound from the S. aureus assays and hopes to have a crystal structure by spring break. She works with Scott Strobel and Michael Cappello, a professor of pediatrics who studies infectious diseases. Benham-Pyle will next assay extracts for activity against hookworm.

Vishnevetsky, the class's other Beckman Scholar, will collaborate with MBB professor John Carlson to find extracts that attract or repel insects. Vishnevetsky chose plants to sample by identifying those reputed to affect insects. Initial bioassays will use fruit flies, but Carlson hopes they will be able to move on to mosquitoes and work with collaborators.

Even after their class commitment has ended, two-thirds of the rain forest students who are still Yale undergraduates continue their research projects and make real scientific discoveries. So far, six papers have been published or are in press, with more on the way, Scott Strobel says. And that's after only a little more than one full year.

I catch up with the students at Yale on a warm, sunny day in late June, the kind of day when the temptation to be outside can be overpowering. Music blares from a boom box in the corner. The students seem content to work in the basement teaching lab that they have appropriated for the summer.

Each student has his or her own bench space, carefully delineated with tape. Their space and their equipment and glassware are identified with personalized tape colors. I wander from bench to bench asking students about their progress.

I've serendipitously chosen a good day to visit. Today is the day that Santiago isolates the first crystals of a natural product from an extract fraction that is active against S. aureus. She is the first person from the 2008 class to obtain crystals. She proudly shows off the tiny red flakes in the bottom of a vial.