Microbes & Human Health

Jim Steele used to be one of the skeptics. He’d be at a conference, listening to early research on the health benefits of probiotics. Steele scoffed at the small experiments. “We would literally try not to laugh in the audience, but we’d laugh pretty hard when we went out that night,” he admits.

But slowly the punch lines gave way to revelation. Steele, a professor in CALS’ Department of Food Science, conducts research on lactic acid bacteria, with a focus on Lactobacillus species. They’re important for human gut health, critical for the production of cheese and yogurts, and are the most common probiotic genus. He knew how incredibly useful they were, but still watched with a humbling disbelief as the data on the health potential of these microbes kept getting broader, deeper and more intriguing.

Our microbiota—what we call the totality of our bacterial companions—is ridiculously complex. Each human harbors a wildly diverse ecosystem of bacteria, both in the gut and elsewhere on the body. They have us completely outnumbered: where the typical body may contain a trillion human cells, your microbial complement is 10 trillion. They have 100 times more genes than you, a catalog of life potential called the microbiome. (The terms “microbiome” and “microbiota” are often used interchangeably in the popular press.)

While our initial, germaphobic impulse may be to freak out, most of these bacterial companions are friendly, even essential. On the most basic level they aid digestion. But they also train our immune system, regulate metabolism, and manufacture vital substances such as neurotransmitters. All of these things happen primarily in the gut. “In many ways the gut microbiota functions like an organ,” says Steele. “It’s extraordinarily important for human health,” with as much as 30 percent of the small molecules in the blood being of microbial origin.

Early research has suggested possible microbiota links to protecting against gastric cancers, asthma, numerous GI disorders, autoimmune disease, metabolic syndrome, depression and anxiety. And the pace of discovery seems to be accelerating; these headlines broke in just a few months last spring:
• Mouse studies suggested that the microbe Akkersmania muciniphila may be a critical factor in obesity;
• Kwashiorkor, a form of severe malnutrition that causes distended bellies in children, was linked to a stagnant microbiota;
• Risk of developing Type 2 diabetes was linked to an altered gut microbiota.

The catch: For all the alluring promise of microbes for human health—and it’s now clear they’re critically important—we have almost no idea how this complex system works.

The human gastrointestinal (GI) tract is a classic black box containing hundreds or thousands of species of bacteria (how many depends on how you define a species). There are viruses, fungi and protozoans. Add to that each person’s distinct DNA and their unique geographic, dietary and medical history—each of which can have short- and long-term effects on microbiota. This on-board ecosystem is as unique as your DNA.

Beyond these singularities, the action is microscopic and often molecular, and even depends on location in the GI tract. Most microbiota studies are done with fecal material. “Is that very informative of what’s going on in the ileum?” asks Steele, referring to the final section of the small intestine, which is thought to be the primary site where immunomodulation occurs. “From an ecosystem perspective, fecal material is many miles away from the ileum. Is it really reflective of the ileum community?”

Meat, With a Touch of Fruit

When Jeff Sindelar talks about the ingredients he’s working with, you’d think he was making juice. Not quite. He’s adding things like cranberry concentrate, cherry powder, lemon extract and celery powder to meat.

But Sindelar, a CALS professor of animal sciences and a UW–Extension meat specialist, is not adding them for flavor. He’s looking at ways to ensure that meat products labeled “organic” and “natural” are safe to eat.

Sales of organic and natural foods are booming, with double-digit percentage gains almost every year. As more and more food processors scramble to meet that demand, they’re encountering a special challenge. Because they must process these meats according to organic and natural label requirements, they are unable to use the vast majority of antimicrobial agents employed in standard meat processing.

“Most ingredients and technologies that serve as antimicrobials—ingredients that can improve safety by either suppressing, inhibiting or destroying any pathogenic bacteria—are not able to be used in products labeled ‘natural’ and ‘organic,’” Sindelar says.

The trick is to find alternative materials and processes that deliver safety—and also offer the look and flavor that consumers value.

Sindelar has identified some options. “A number of different natural-based organic acids offer a significant improvement to food safety,” says Sindelar, who is working in partnership with Kathy Glass, associate director of the CALS-based Food Research Institute. “We have tested a number of different ingredients such as cranberry concentrate, grape seed oil and tea tree extract.”

Some compounds from natural sources work as well as such standard preservatives as sodium nitrite, sodium lactate or sodium diacetate, to name a few. But it can take heavy doses of some natural ingredients to provide equivalent results—causing some undesirable side effects.

“Cranberry concentrate is a very effective natural antimicrobial,” says Sindelar. “But if you use the amount needed to significantly control the growth of bacteria, the meat turns cranberry red.”

Part of the researchers’ work involves “challenge testing”—adding pathogenic microbes to the meat to make sure that a given ingredient prevents the growth of bacteria throughout processing and storage. If substantial numbers of microbes grow, that ingredient is ruled out as being an effective natural antimicrobial.

Successful tests have already led to new products. Cherry powder combined with celery powder, for example, “is already being adopted by processors because of how effective these ingredients are in improving meat safety and quality,” notes Sindelar. And the search for other natural additives continues.

Both researchers are certain they’ll find success—particularly as they continue working in partnership with producers in the field.

“Collaborative research between the university and industry is essential to understand the synergistic effects of these ingredients—and to ensure the safety and quality of natural and organic meats,” says Glass.

Protecting our Pollinators

People and bees have a long shared history. Honeybees, natives of Europe, were carried to the United States by early settlers to provide honey and wax for candles. As agriculture spread, bees became increasingly important to farmers as pollinators, inadvertently fertilizing plants by moving pollen from male to female plant parts as they collected nectar and pollen for food. Today, more than two-thirds of the world’s crop plants—including many nuts, fruits and vegetables—depend on animal pollination, with bees carrying the bulk of that load.

It’s no surprise that beekeeping has become a big business in the farm-rich Midwest. Wisconsin is one of the top honey-producing states in the country, with more than 60,000 commercial hives. The 2012 state honey crop was valued at $8.87 million, a 31 percent increase over the previous year, likely due in part to the mild winter of 2011–2012.

But other numbers are more troubling. Nationwide, honeybee populations have dropped precipitously in the past decade even as demand for pollination-dependent crops has risen. The unexplained deaths have been attributed to colony collapse disorder (CCD), a mysterious condition in which bees abandon their hives and simply disappear, leaving behind queens, broods and untouched stores of honey and pollen. Annual overwintering losses now average around 30 percent of managed colonies, hitting 31.1 percent this past winter; a decade ago losses were around 15 percent. Native bee species are more challenging to document, but there is some evidence that they are declining as well.

Despite extensive research, CCD has not been linked to any specific trigger. Parasitic mites, fungal infections and other diseases, poor nutrition, pesticide exposure and even climate change all have been implicated, but attempts to elucidate the roles of individual factors have failed to yield conclusive or satisfying answers. Even less is known about native bees and the factors that influence their health.

Poised at the interface of ecology and economy, bees highlight the complexity of human interactions with natural systems. As reports of disappearing pollinators fill the news, researchers at CALS are investigating the many factors at play—biological, environmental, social—to figure out what is happening to our bees, the impacts of our choices as farmers and consumers, and where we can go from here.

Mystery Solved

White-nose syndrome, a fast-spreading disease that over the past six years has been decimating bats in North America, is caused by the fungus Geomyces destructans, scientists at the USGS National Wildlife Health Center in Madison have proven. Their work provides the first direct evidence that G. destructans is responsible for the disease.

Researchers from the U.S. Geological Survey, CALS and other institutions showed that all little brown bats exposed to G. destructans in their study developed white-nose syndrome while hibernating in captivity.

“Identifying G. destructans as causing the disease will help direct future research toward elucidating what makes the fungus pathogenic, what makes North American bats susceptible—and what environmental factors are important for disease progression and transmission to take place,” says Jeffrey Lorch, who was part of the research team as a forest and wildlife ecology graduate student in the UW–Madison Molecular and Environmental Toxicology Center.

Bat populations in the eastern U.S. have been declining at an alarming rate since 2006, when white-nose syndrome first appeared in New York state—a development of particular concern to the U.S. agricultural industry, which saves billions of dollars in pest control costs each year courtesy of insect-eating bats. Bat declines in the Northeast already have exceeded 80 percent.

As Lorch points out, understanding what causes the disease is a crucial first step in controlling it.

Tech Transfer Showcase

When CALS biochemistry professor Harry Steenbock experimented with vitamin D in the early 1920s, his work proved groundbreaking in more ways than one.

Steenbock’s discovery that he could increase the vitamin D content of foods through irradiation with ultraviolet light eventually eliminated rickets, a then-common and often deadly disease characterized by softening of the bone due to vitamin D deficiency.

With his own $300, Steenbock patented his discovery and offered it to the University of Wisconsin. When the university declined, Steenbock conceived of the idea to form a foundation to collect, invest and distribute money earned through research-based discovery—
a pivotal step in establishing the Wisconsin Alumni Research Foundation (WARF), the nation’s first university technology transfer office. WARF’s first licensing agreement with Quaker Oats in 1927 led to the fortification of breakfast cereals with vitamin D.

Since then WARF has patented nearly 2,000 university inventions. And—in the grand tradition of Steenbock—many of them stem from the labs of CALS scientists and alumni. Here we present some highlights from recent years.

Deltanoid

Though the term biotechnology was little known in his time, Steenbock was one of the world’s first biotechnologists—and he passed on that torch to his gifted graduate student, Hector DeLuca.

The path was not always smooth, and DeLuca hit some obstacles when his own seminal work on vitamin D in the 1960s led him to WARF. When he discovered the active form of vitamin D and chemically identified its structure, he was unable to file a patent due to unwieldy government restrictions. DeLuca eventually obtained a patent with the help of WARF patent attorney Howard Bremer and some influential people in Washington. That same group worked with federal legislators on the 1980 Bayh-Dole Act, which allowed nonprofit organizations to obtain patents spurred by federally funded research. As a result, WARF now holds more than 200 active patents from the DeLuca lab.

DeLuca is the founder of three spin-off companies, each stemming from his vitamin D work. Bone Care International, a maker of drugs to treat dialysis patients, was sold in 2005 to the biotech firm Genzyme for nearly $600 million. A second company, Tetrionics (now SAFC Pharma), was acquired by Sigma Aldrich Fine Chemicals in 2004 for close to $60 million.

Now DeLuca’s main focus is Deltanoid Pharmaceuticals, which he founded nearly 10 years ago with his fellow biochemistry professor (and wife) Margaret Clagett-Dame. The company is testing various vitamin D derivatives against osteoporosis, psoriasis, and kidney and autoimmune diseases, as well as other types of compounds to treat kidney failure. In clinical trials one vitamin D derivative seems to be highly effective in stimulating bone growth, and a number of other Deltanoid products are nearing the human testing phase.

With a business office located on Madison’s Monroe Street and about 10 employees, DeLuca describes Deltanoid as small but tenacious. “Our plan is to keep the company lean and mean until it has an income of its own,” he says.

TRAC Microbiology

Food contamination outbreaks generate headlines, especially when they result in illness or death. Virginia Deibel, while still a graduate student in food science and bacteriology at CALS, combined her interest in both subjects by forming TRAC Microbiology, a company that helps keep our food supply safe.

Deibel describes how it felt when TRAC played a pivotal role in identifying the type and location of bacteria that forced a shutdown in a large meat processing plant. The culprit turned out to be Listeria monocytogenes, the same bacteria that recently killed several dozen people who ate contaminated cantaloupes.

“We went in and found where the bacteria were harboring, removed it and tested that it was effectively gone. We then rewrote the client’s food safety programs, retrained all their employees and presented our corrective actions to the USDA,” Deibel recounts. “During the retraining phase I had employees coming up to me and thanking me for reopening the plant, which impacted entire families. That made me realize what we could do for a community.”

Deibel founded TRAC (for Testing, Research, Auditing and Consulting) 12 years ago. She was less than 18 months away from completing her Ph.D. when she began redirecting her energy toward writing a business plan and securing a start-up loan of $400,000.

“I knew from my work as a food scientist that there were many smaller companies that needed help with food safety,” says Deibel. “They simply did not have the necessary infrastructure to implement food safety systems.”

Initially TRAC services included helping food plants develop and update their food safety systems, train their quality assurance personnel and provide scientific justification for such practices as freezing, packaging and adding preservatives.

“Our original goals were to conduct research projects and provide food safety consultations,” says Deibel. But she soon discovered that many small food companies needed testing to meet customer requirements. That need inspired Deibel to expand its testing services, and TRAC, which eventually grew to 30 employees, soon succeeded in attracting larger clients from around the region.

Last fall Covance, one of the nation’s leading bioscience companies, announced the acquisition of TRAC Microbiology. Covance had paid close attention to TRAC and tapped Deibel to head development of its own food safety consulting division.

“Covance has excelled in so many different arenas—drug development, nutritional chemistry. I’m enjoying the challenge of helping such a respected company develop and grow a food microbiology arm,” says Deibel.

Sabrina R. Mueller-Spitz

Mueller-Spitz’s interest in soil led to a fascination with the microbial communities found there—and to a Ph.D. in microbiology. As a professor at the University of Wisconsin–Oshkosh, Mueller-Spitz imparts those interests to her students. “My favorite part of teaching is fostering wonder and providing a wider understanding of new topics in microbiology, environmental problems that threaten human health and understanding how epidemiology is used to assess and improve human health,” she says.

The Infection Eaters

Bacteriologist Marcin Filutowicz specializes in developing antimicrobial technologies that one day may help replace antibiotics—and save lives—as the power of our antibiotics arsenal wanes. But he doesn’t stop there. Filutowicz has founded or co-founded three biotech companies to help ensure that his technologies actually make it into the world’s hospitals. The idea for his newest venture, Amebagone, founded this year, sprung from his work investigating a collection of soil-borne amoebas assembled decades ago by UW bacteriologist Kenneth Raper, who is best known for helping ramp up penicillin production in time to save thousands of soldiers wounded during World War II.

Grow Magazine: Let’s start with the basics. What’s an amoeba?

Amoebas are unicellular organisms. They are not animals or plants or bacteria. They are protists, which is a whole separate group. And what they do, their sole purpose in life—as much as we can say—is to feed on bacteria. So this is their primary source of sustenance, and once they eat all of the bacteria in their environment they yell at each other—using chemical signals—and gather together.

On the Petri dish, you can see them swarming when they decide to aggregate. Initially, they form something that looks like a slug. It’s a community of a million or so amoebas that are packed together into a sack. The slug moves around looking for more food. If it can’t find anything to eat, the slug transforms into stalks and spores that get distributed by the wind. When the spores land on moist soil, they germinate and start eating the bacteria in the soil, and the process repeats itself.

How did you start working with these organisms?

For one of my companies, PlasmiGon, we needed access to libraries of small molecules to be successful. After screening a few libraries that were available to me, I started thinking about other potential sources of small molecules, and I realized that Ken Raper, who established the whole field of amoeba studies, had left a huge collection of amoebas in our department. This collection involves over 1,000 different amoebas gathered from five continents and several island nations. So it’s extremely diverse in terms of the geographical locations. It represents a huge resource of diversity of small molecules.

So my take was, why don’t we start reviving these amoebas and come up with techniques to look for useful small molecules produced by them? So we started opening those samples, some of them 70 years old. And then the issue was, well, how do you propagate them? Because, to be honest, I knew nothing about amoebas.

I went to a colleague and asked, “How do you grow these beasts? Do you grow them like bacteria?” And he said, “You feed them with bacteria.” The moment he said that—“You feed them with bacteria”—I went back to my office and I quickly computed all of the information I had learned over the past few days. I realized that this could be a new biotherapy because the particular amoeba we wanted to grow, Dictyostelium discoideum, is benign. There was no single report of it having adverse effects on humans, animals or plants. It’s an organism that you simply put alongside bacteria, and they do nothing else but eat it. I disclosed this to WARF in 2009, but they turned my disclosure down.

That’s surprising.

Not really. At the time, we didn’t have any proof-of-principle, no data, nothing. It was just an idea. But I decided that I could not let it die. I decided to form Amebagone and let that company patent the technology.

How do you picture amoebas being used in medicine?

Right now we’re focused on methicillin-resistant Staphylococcus aureus (MRSA). This MRSA is a major agent of nosocomial infections in hospitals. It kills a lot of people. And it happens that two billion people on this planet carry staph in their nostrils. It is part of our natural biota. They inhabit a very narrow area in our nostrils that has just the right temperature and salinity, so they are not all over. They are compartmentalized in a band or section of the nostrils.

And we all touch our noses. We can’t help it. As we touch, there’s moisture in there, and so we contaminate our fingertips. And after surgery, it’s natural to want to see the wound, and in many cases people accidentally self-contaminate the surgery site just by lifting up the dressing to look at it.

But if we can deliver amoebas to the nostrils pre-surgery, we can essentially decontaminate the nostrils of undesirable microbes. We did proof-of-principle experiments with MRSA, and amoebas eat MRSA like crazy. So even though antibiotics cannot kill MRSA, amoebas can.

O Bioneers

It wasn’t exactly panning for gold, but a lesson in “bioprospecting,” as it’s called, had students scour the campus looking for something just as valuable: invisible forms of life that could one day be key in developing a sustainable alternative to oil.

“Instead of going out and looking for precious metals, we’re looking for precious microbes,” says John Greenler, director of education and outreach at the Great Lakes Bioenergy Research Center and lead instructor of the university’s first bioenergy course for freshmen, held this past fall semester.

“Out in the environment there are a lot of microorganisms that are really good at breaking down fibrous plant material,” Greenler notes—a vexing but essential step in producing biofuel.

“Before I took this class I was only a little curious with the concept of bioenergy. Now I feel involved with bioenergy research and the possibility of using it to solve many environmental, political, and economic problems.” -Michael Polkoff

“We’re hoping to figure out how those microbes do that and then utilize that process to make biofuels—essentially, capture energy for our transportation needs the same way the microbes capture energy as a source of food,” Greenler says.

“Bioenergy: Sustainability, Opportunities and Challenges” debuted as a First-Year Interest Group (FIG) program open to 20 freshmen, and it was snapped up quickly during registration. As the bioprospecting lab shows, the course was designed to have students work on real-world problems researchers face in a new and rapidly growing field.

That includes the frustrations. Student Michael Polkoff reports that the prospecting material chosen by his group—pond scum—came up negative for microbes that produce cellulose-busting enzymes.

“While the results are depressing for the work we put into this—especially going barefoot into a freezing, sludgy drainage pond—it’s part of doing scientific research,” says Polkoff. “Sometimes you get results, other times you don’t. More importantly, we learned how research is done.”

The course has galvanized Polkoff’s interest in bioenergy. “Before I took this class I was only a little curious with the concept of bioenergy,” he says. “Now I feel involved with bioenergy research and the possibility of using it to solve many environmental, political, and economic problems.”

The course is offered through a partnership between the Great Lakes Bioenergy Research Center and the Wisconsin Bioenergy Initiative. Students visit the UW campus labs of some of the nation’s foremost researchers, and one field trip took them to CALS’ Arlington Research Station to study bioenergy field plots.

The FIG program, which clusters three courses linked by a common theme—the bioenergy course was paired with introductory chemistry and environmental studies—targets low income, minority, “first in family to college students,” says Greenler. “Overall, about 30 percent of students in the FIG program are minorities.”

When the Deep Freeze Thaws

AFTER FOUR DECADES STUDYING some of the planet’s coldest soils, James Bockheim has gained a formidable vocabulary to describe the interplay between ice and soil. Analyzing a core of permafrost—the permanently frozen soils found near the Earth’s poles and on some mountaintops—he points out vein ice threading the length of the core. He speaks of cryoturbation, the mixing of soil layers caused by freezing and thawing ice, and notes the formation of lens ice, puck-like discs that form above the permafrost layers.

These features make permafrost samples beautiful, often resembling the mixed batters of a marbled cake. But they also have important implications for the planet’s climate, says Bockheim, a CALS professor of soil science. Although permafrost and other cold soils make up only 16 percent of all soil, they hold 50 percent of all soil carbon, making Arctic soils a deep freezer for vast stores of the greenhouse gas. But many researchers fear that as global warming thaws permafrost layers, that carbon will be released into the atmosphere, exacerbating changes in climate.

Bockheim and Kao-Kniffin are trying to glimpse into the future of polar soils by learning from their past.

Last spring, that question took Bockheim and postdoctoral researcher Jenny Kao-Kniffin to Barrow, Alaska, which at 320 miles north of the Arctic Circle is the United States’ northernmost city. It’s a region that already feels acute pressure from climate change. According to Bockheim, temperatures around Barrow have risen by as much as 2 degrees Celsius during the past 20 to 30 years, nearly four times the rate of warming for the planet as a whole. Thawing soils have put houses, roads and even the Alaskan oil pipeline at risk of collapse. But the changes in Barrow have implications that reach far beyond the Arctic, says Bockheim.

In Barrow, Bockheim and Kao-Kniffin are trying to glimpse into the future of polar soils by learning from their past. Working with a team of international scientists, they have been digging into the soils of former lake basins, which drained anywhere between 50 and 8,000 years ago, to get a view of how different soils have developed over time. Once emptied of water, Bockheim explains, the basins fill with grasses, sedges and willows, attracting animal life and creating changes in soil composition. Older beds contain more carbon, for instance, and they also harbor more ice, due to repeated seasons of snow and rain trickling into upper layers of soil.

The scientists’ interest is not only in the soil itself, but also in the microbes that call it home—specifically, how those resident microbes metabolize sources of carbon in the soil. One of the main concerns about the warming Arctic soils is that as once-frozen organic matter thaws, resident microbes will start churning out carbon, releasing potentially large quantities back into the atmosphere. But it’s also possible that the soil nutrients won’t be suitable to support the microbial community.

“We know the rate of carbon sequestration in these lakes, but we don’t know anything about decomposition rates and the different forms of carbon that exist,” says Bockheim, whose study of polar soils began with a trip to Antarctica in 1969.

Kao-Kniffin, a microbiologist who recently became an assistant professor at Cornell University, is now in the process of characterizing the microbial community that lives in the Alaskan soils. She will analyze fatty acids and DNA of the soil microbes to get a clearer picture of their metabolic function, using stable isotope tracers to follow the path of carbon through the system.

“The lab component is easy,” says Kao-Kniffin, compared to the physical ordeal of drilling and collecting cores from the Alaskan tundra. Once samples were collected, the scientists returned to a small Quonset hut backdropped by the frozen Arctic Ocean to measure and prepare them for lab analysis. At one point, as newly thawed soil samples dried in an oven, a whiff of a mushroom-like aroma wafted through the hut, a sign of the fungi and other microbes in the soil. It was a small reminder of the suspended life harbored within those frozen soils—and the potential consequences once that life is awakened.

Baby on Board

At age two and a half, K.C. Kniffin knows something you might not know about the Arctic Circle: The snow there is not good for packing snowballs. He also knows how much fun it is to breeze across the tundra on a snowmobile, or “snow-nobile,” as he prefers to call it.

Not many preschoolers from the Lower 48 get to become Arctic explorers, but K.C. got his chance courtesy of Moms on the Go, a CALS fund that covers some travel and childcare expenses for researchers out in the field. In K.C.’s case, the fund covered airfare for his father, Kevin Kniffin—the husband of microbiologist Jenny Kao-Kniffin—when she was doing postdoctoral research in Barrow, Alaska with CALS soil scientist Jim Bockheim.

Kniffin provided childcare for K.C., often playing with him in the snow just a few yards from where mom was doing research. The intent of the fund is to spare families the pain of extended separation and parents the usual load of worry and guilt about leaving their children behind. Instead, families get to flourish in each other’s company in exciting (if often challenging) new surroundings.

According to Jenny Kao-Kniffin, it’s a win-win for everyone. “My son helped us work longer hours with less stress,” she says. “Barrow is in a very remote location and resources are scarce. Having my son with me was the best form of entertainment for the entire research team. It’s amazing how everyone’s mood improved when my son was present.”

Kao-Kniffin, now an assistant professor at Cornell, puts Moms on the Go in the context of other progressive developments at CALS that support women in the workplace.  “The Microbial Sciences Building also has a lactation room and creative conversational areas. It was a great place to meet an amazing collection of women scientists that prove you don’t have to choose between your family and your career,” she says.

The UW Foundation maintains more than 6,000 gift funds that provide critical resources for the educational and research activities of the college. To help support Moms on the Go, visit http://www.supportuw.org/.

My Own Miracle Drug

In this issue, you’ll read an update on a topic that has special significance for me. Antibiotics saved my life.

When I was 13, I was diagnosed with a potentially fatal staph infection. This is a sneaky and dangerous bug, and by the time the infection was detected and recognized, I was critically ill, facing major surgery and an uncertain recovery. My only hope for recovery was the drug dicloxicillin, which was prescribed and administered in massive doses. It worked. And I survived, one more life saved by these miracle drugs.

It’s hard for most of us to imagine a world without antibiotic pharmaceuticals. But if we are not careful, we may find ourselves much too close to that world again.

Today, it is hard for most of us to imagine a world without antibiotic pharmaceuticals. And yet it’s been considerably less than a century since they were recognized and introduced into clinical use, thanks in no small part to pioneering work on our campus. But if we are not careful, we may find ourselves much too close to that world again. The rising levels of microbial resistance to our best antibiotics—and the dearth of new antibiotics in the drug pipeline—are a startling wake-up call that could imperil our ability to treat disease in humans and animals.

Fortunately, we’ve heard that wake-up call. At CALS, we have one of the brightest and most creative communities of microbiologists in the world, and they are fast uncovering promising new antibiotic compounds. But they are doing more than that. By taking the next step and refining the compounds that may be significantly valuable in clinical use, they are advancing a new model of drug development that can channel more of these medications into the marketplace, where they can save more lives.

To me, this work offers a wonderful illustration of how our college continues to do what it was invented to do—to create real, lasting change in people’s lives. Research does have the capacity to save millions of lives, and I am living proof of that power.

What's in the Water?

SHARON LONG is an associate professor of soil science in CALS, but that title only hints at her multidimensional role for the university and the state. As director of environmental microbiology for the Wisconsin State Laboratory of Hygiene, Long runs a public-service unit that analyzes some 60,000 water samples each year, part of the state’s effort to keep its wells and drinking water safe from microbial contamination. As if that weren’t enough to keep her busy, she has appointments in UW-Madison’s Nelson Institute for Environmental Studies and the College of Engineering’s civil and environmental engineering department.

What’s with all of your titles?

Well, my work is very interdisciplinary. When you’re talking about tracking pathogen sources in water-and keeping them from reaching people-you need access to people with a bunch of different backgrounds. You need people who understand microbiology. You need people who understand public health. You need people who understand laboratory testing. And you need people who can solve problems. One of the things I really like about Wisconsin is that it’s so interdisciplinary by nature. I can have a foot in all of these camps and hire students from each of those areas.

My role is to bring in the tools that allow us to figure out what might be making a water sample unsafe and how the pathogens got there.

Your work with the State Laboratory of Hygiene is very applied. Is it common for a professor to have that role?

Yes, that’s been the tradition. The lab is technically part of the university, and they always try to have a strong connection to the research community here. My role is really to bring in the research perspective-to bring in the tools that allow us to figure out what might be making a water sample unsafe and how the pathogens got there.

Where do the samples come from?

All over the state. The lab is a client-based service, and so anyone can send a sample in to be analyzed. We get a lot of samples from private well owners who want to be sure that their well hasn’t been contaminated by animal waste or other things. And we also test for a number of municipalities, including Madison and Milwaukee.

Is this routine testing, or are you investigating problems?

It can be both. For instance, we did a lot of testing after the floods last summer. When people came back to their homes, many were worried about flood waters going over the tops of the wells, and a fair number of those tests did come back unsafe.

What happens then?

Well, in that case, we worked with the Department of Health and Family Services and the Department of Natural Resources to get information out to people in the affected areas. Generally, the first thing they do is super-chlorinate the well and pump it through. Then, if it comes back contaminated again, we try to find out what’s in there and where it may be coming from. We start looking to see if there’s a continuing source of contamination.

And that’s where your research comes in.

Right. The first level of testing generally just tells you about the presence or absence of coliform bacteria, which we use as a broad-level indicator because they live in almost every warm-blooded animal. So that test tells us that we may have some kind of contaminant getting into the water supply. Then the question becomes what kind of contamination we’re dealing with and in what quantity. There is a standard set of microorganisms we can look for, and that’s the path that pretty much any public-safety lab would follow.

But if the question becomes about more than just identifying the particular pathogen, we do have some tools that allow us to start to figure out where the pathogens came from. The field is called microbial source tracking, or MST. We have tests that can tell us whether the source of the pathogen was human or non-human, and there are even some tests that allow us to go deeper than that and ask what kind of animal was the source of the contamination. For example, we can do a test where we discriminate between grazing animals and all other animals, which could tell us if the contamination was coming from a nearby farm or some other source.

How can you tell?

Every species of animal has a unique intestinal environment and therefore a unique mix of microorganisms that live in that environment. The idea is to use some high-level microbiology to identify differences in the microorganisms that can tell us where they lived. So if we have contamination in a new residential development that is located next to an active swine farm, you want to look at those microorganisms and figure out whether they came from humans or pigs. If it’s humans, you would want to look at the septic system as a likely source of contamination, but if it’s pigs, you’d try to see if animal waste was contaminating the water supply.

It sounds like CSI.

It is. But really, it has only been within the past 10 years that science has progressed enough to do this. People have been studying source tracking since the 1970s, but we’re finally getting to the point where we can apply it with some level of certainty.

I understand you’ve used this technology recently in a contamination problem at a restaurant in Door County. Can you tell me more about that case?

Yes, that was really fascinating. This was a brand-new restaurant in one of the popular vacation areas up there, and not long after it opened, a number of people got sick. The concern was that since there was a lot of agriculture in the area that maybe there was contamination from animal waste. But when we applied our source tracking, we found human markers, meaning that it had to be a human source. It turned out that a pipe from the septic holding tank was not hooked up properly, and the sewage was going straight down into the aquifer and reaching their well.

Do you think pegging the source as human helped identify that problem?

Certainly, because it put the focus on the septic system. It was a brand-new system, and it was very well designed, so there wasn’t much reason to suspect it would be a problem. But the test caused the county to go back and reevaluate it. I hear the restaurant has since put in a state-of-the-art system for treating its well water. They’ve probably got the cleanest water in Door County now.

That’s good news. But seeing all these cases of contamination-does it ever make you think twice about drinking tap water?

Not at all-at least not in this country. One of the societies I belong to is the American Water Works Association, and at their annual conferences they actually pay extra to make sure that all of the water bottles are filled with tap water. We’ve got great water, and I never think twice about it.