Story by Joel Smith; photos by Rajah Bose
A junior in college, Vina Tran already has a bona fide scientific discovery to her name. Go ahead and look her up on the Actino-bacteriophage Database, a compendium of biological findings maintained by the University of Pittsburgh. Her name (and that of Gonzaga University) appears for having discovered “Marty,” a microscopic virus she and her lab partner dug up in the flower beds outside of Hughes Hall.
The name alludes to all the Egg McMuffin sandwiches she and her lab partner consumed during morning classes, but this is no A-for-effort, gold-star funny stuff. It’s the study of an organism that no one in the world had ever found before, and its inclusion in the database is helping scientists better understand these viruses and their overlooked role in our ecosystem.
And Tran is not alone. In fact, a paper published in the peer-reviewed journal eLife in 2015 counted 130 Gonzaga biology students among its authors. All were credited with the discovery and analysis of six viruses known as “phages,” and all can now call themselves published scientists. Tran and her peers are part of a pioneer program taking place at Gonzaga and about 80 other institutions around the country that is both furthering the field of viral research and changing the rules for how undergrads study science.
The program, conceived by University of Pittsburgh biotech Professor Graham Hatfull and funded by the Howard Hughes Medical Institute (it arrived at Gonzaga in 2010), is called Science Education Alliance-Phage Hunters Advancing Genomics and Evolutionary Science, or SEA-PHAGES, and the object is to dig up, isolate, identify and genetically sequence invisibly tiny viruses called bacteriophages.
Never heard of them? They’re only the most numerous form of life on the planet.
The Enemy of Our Enemy
Called the “dark matter of the biological universe” in that eLife report from 2015, bacteriophages (literally “bacteria eaters”) are minuscule viruses that break into the cells of bacteria, hijacking their machinery and multiplying. And as anyone who has ever packed a bottle of Purell on the bus knows, bacteria are everywhere.
“We humans have bacteria on our skin, we have bacteria in our gut,” says Gonzaga biology Professor Kirk Anders, who has helped spearhead the phage program, “so everywhere you find bacteria, people find phages that live there, too — infecting and living right along with the bacteria.”
“You just have to let the science guide them, and be OK with a little bit of mayhem, because that’s how [students] learn.”
(Professor Marianne Poxleitner)
Freaked out yet? Don’t be. Not only do phages not pose a health threat to humans but their taste for bacteria means that they actively destroy organisms that could pose a threat to us — like the bacteria that cause tuberculosis and leprosy. “The enemy of our enemy,” science writer Carl Zimmer called them in his book “A Planet of Viruses.”
“The more we know about bacteriophages and how they work and how bacteriophage genes work, the more that we could have power over being able to use them against bacteria,” says Anders.
That could be especially important as bacteria begin to develop resistance to antibiotics — our standard weapon against them. “I think phage therapy is going to become more important sooner rather than later,” says Gonzaga biology Professor Marianne Poxleitner, who has taught a course on the biomedical applications of phages. But she emphasizes that that day could still be decades off, and admits that the save-the-world angle is really only used to get students excited about the potential for their work. “We really try to get students to not focus in on the direct applications of this research. We try to tout it more as basic science and genetics.”
Tackling phages’ mind-bending diversity is the first hurdle to understanding how they work, and how to put them to use. Because they number around 10 to the 31st power, and because their short lifespans see the entire population turn over every few days, theirs is a mammoth — and constantly adapting — family tree to outline.
But that’s where Tran and other undergrads in the program come in.
Meet Your Virus
Since the establishment of the Sea-Phages program at Gonzaga in 2010, science students spend their first-year Intro to Biology course finding a phage (those flower beds outside of Hughes are a particularly hot spot), growing more of them in a petri dish, isolating them, and purifying their strain. Once they have a good sample (and a snazzy name), their phages are sent to the electron microscope at Washington State University, and when the photos come back, the students finally get to see — after almost an entire semester — what their pet phage actually looks like.
The following year, students going on to take Genetics will pick up where they left off in Biology, often even studying the same individual phage that they discovered as first-year students. In this course, they clone their phage’s DNA and eventually produce a complete DNA analysis of its genome, posting their findings to a database that other “real” scientists can query and use in their own research.
Students who are especially “jazzed by viruses,” as Anders says, can even go on to further courses — digging deeper into the genome, doing molecular research, and conducting “real experiments interesting to other people.”
But finding phages is really only half the equation. While these undergrads’ discoveries are contributing to a scientific body of knowledge, and while their data could one day contribute to life-saving treatment, the real magic of the program, say Anders and Poxleitner, is in the difference between this and every other run-of-the-mill introductory science lab.
Just ask Gonzaga senior Nick Braukmann. He was a good student in high school. He’s well-spoken. He took all of the AP science classes. And he arrived at Gonzaga with at least a rough idea of what he wanted to do with his life.
But then he signed up for Intro to Biology.
“In traditional-style labs, they give you an experiment and you are done with it in that one class period,” he says. But here, “they made it sound like they had no idea what was going on, and we were all going to fi gure it out together. … [That] was very new to me.”
That’s the point, says Anders.
“A typical introductory lab used to be a place where students would go in, maybe repeat classic experiments that other people have done, as a way of demonstrating some concept,” he says. “But in recent years, even 20 years ago, people started to say there’s more to science than just learning facts. And there was a big movement toward inquiry-based labs. Get students in and [give] them a feel for what it’s like to actually not know what the answer’s going to be. … And then engage students in the scientific process.”
Tran found that exhilarating.
“The professors didn’t know where this was going to go, we didn’t know. It was just a general guideline: This is your goal. Get there,” she says. “It was nice to have a program where professors don’t have all the answers, to go on that journey with them.”
“Whether you get an answer, whether you don’t, you’re doing real research,” says Braukmann, “and this is what your career would look like.”
Braukmann, who named his phage “Charm” because it took him three tries to dig up a unique specimen, went on to study his own phage in subsequent classes, and he adds that that continuity also is something you don’t often find in conventional science programs.
Of course, not all students are comfortable with the responsibility that real science places upon them, says Poxleitner, the biology prof.
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“When you’re annotating [the genome], they keep asking us ‘What’s the answer?’,” she says. “They struggle with this idea of not knowing enough. They struggle with having the authority to make that scientific decision. Once they get used to it, they like it.”
Poxleitner adds that even teachers can struggle with the shift in classroom approach. She spent her recent sabbatical in Maryland at the Howard Hughes Medical Institute — the organization underwriting the phage program nationwide — teaching other professors how to bring the results seen on Gonzaga’s campus back to their own campuses.
“Some of it is teaching science, but a lot of it is trying this idea of the pedagogy, and getting them excited about getting away from the cookie cutter,” she says. “Everybody’s nervous. You’re learning something new, and honestly, it’s been a while since we’ve had to learn something like this. The hardest thing is that not every student is at the same stage in the classroom. On a given day, you could have five students doing five different kinds of experiments. And you just have to let go, let the science guide them, and be OK with a little bit of mayhem, because that’s how [students] learn.”
Erin Lapsansky would agree with that. The 2014 grad (pet phage: “MamaJanJan”), who now works at Colorado State University’s Center for Rhizosphere Biology, says that the mayhem of real science made her more rigorous about protocol and keeping a perfect lab notebook, and more realistic about what her future as a scientist would look like.
“One thing that really hit home for me is that science is not on your schedule, and it is defi nitely not a 9-to-5. Some days science puts you in the lab for 18 hours. Some days you sleep in the lab. Sometimes you have nothing to do but wait,” she says. “[The phage program] really prepared me for this because it was twice a week on the schedule, but I often had to come in on the weekends or early in the morning to accommodate the scientific process.”
Alex Murphy, a 2015 grad who found her phage, “Phanphagia,” in a flower bed outside Cardinal Bea House, says the trial and error of real science came with responsibilities she wasn’t used to.
“If I found something that didn’t make sense, then it was up to me to think of an explanation and come up with a hypothesis. It was the fi rst time I was really forced to think creatively about science,” she says. But ultimately she had the pleasure of being “the world’s leading expert” on her particular phage. “I started taking initiative, bringing the ‘Phoxy’ genome home, annotating it in my free time, and reading scientific papers for fun.”
Murphy is now working on a Ph.D. in genetics at the University of Wisconsin-Madison.
“In hindsight, the phage lab is what spurred my interest in science and research,” she says. “It is where I realized that science is so much more than memorizing vocab words or mindlessly cutting open a squid and answering fill-in-the-blank questions. It is where I started to understand the importance of being curious and of being persistent, even in the face of failure.”
Tran still has another year to go at Gonzaga, but she’s already looking ahead.
“A program like this is so important because it fosters growth for us, it lights a fire,” she says. “I want to spend the rest of my life doing this.”