A Precise Hope

Mason Konsitzke is 7. He loves food (especially when he can share it with others) and anything military (both of his grandfathers served). He likes to fly kites and play with his 5-year-old sister, Alexandra. But Mason was born with a disease called neurofibromatosis type 1, or NF1, and each day can present new challenges for him and his family.

NF1 is a genetic disease caused by changes, or mutations, to a single gene in the human DNA library. Roughly one out of 3,000 babies born in the United States has it. That’s more than three times the incidence of cystic fibrosis, a much better-known condition. Yet few people have heard of NF1.

Mutations in the NF1 gene cause defects in the neurofibromin 1 protein, which acts as a tumor suppressor. Children with NF1 can develop painful tumors along their nerve tracts, sometimes in their skin and in their eyes, which can render them blind. They are often diagnosed with autism spectrum disorder, though not all children with NF1 also have autism, and they are sometimes diagnosed with attention deficit hyperactivity disorder. They may have soft bones that bend and break easily. They are at a higher risk for cancer. And there is no cure.

It was not a disease Mason’s parents, Charles and Malia Konsitzke, had ever heard of. As a newborn, he was healthy, but when Mason was 6 months old, the couple began to suspect something was wrong. Mason developed coffee-and cream-colored spots all over his body, which his father later learned are a hallmark of NF1. Mason received a genetic diagnosis of the disorder just before his first birthday.

“We were like deer in the headlights,” Malia says. “We were in shock, wondering, what does this mean for us? What does it mean for Mason?”

At 18 months, Mason began to lose his ability to speak. He was falling over, screaming constantly, and deliberately banging his head. That’s when an MRI revealed a tumor called a plexiform neurofibroma in a mesh of nerves in the left side of his face. It was growing fast.

A Father and Science Facilitator

Charles (who goes by Chuck) is a research administrator and the associate director of UW–Madison’s Biotechnology Center, a sort of one-stop shop for scientists in need of DNA sequencing, genome editing, and other services.

Upon Mason’s diagnosis, he began to delve into published NF1 research. He wanted to know where it was happening, who was doing it, and how he might be able to help. He sought opinions from experts, wondering how the field could be improved. Many identified the same bottleneck: the lack of a good research model.

In biology, research models are animals, cells, plants, microbes, and other living things that allow scientists to study biological processes and re-create diseases in order to better understand them. Good models yield information relevant to humans, but the right model can sometimes be difficult to find.

A breed of pigs called Wisconsin Miniature Swine was created by a team of UW–Madison scientists to help better model and understand human diseases, including NF1. Photo by Jeff Miller

NF1 is especially complex, affects many systems of the body, and touches many areas of scientific inquiry, from cancer research to neurobiology. Chuck began to search for a better model and, in 2013, when Mason was 3, he settled on pigs. Pigs are similar to humans in many ways that other common research animals, such as mice and fruit flies, are not. That includes their size, which means drugs and devices that work on humans can also be tested on pigs. They have a robust immune system, which rodents lack. And they’re intelligent, so scientists can study changes in their cognition.

Knowing all of this, Chuck went on the hunt for researchers who studied swine.

Braving the Risks

Dhanansayan (Dhanu) Shanmuganayagam BS’97 PhD’06, assistant professor of nutrition and animal sciences at CALS, has spent most of his career using swine to study human diseases, particularly heart disease. In fact, he and colleagues in the animal sciences department created the Wisconsin Miniature Swine, a pig that, like people, can develop heart disease under the right conditions.

Dhanansayan “Dhanu” Shanmuganayagam describes his research during a Neurofibromatosis Type 1 (NF1) symposium for patients and families held at the UW–Madison Health Sciences Learning Center in May 2017. Photo by Jeff Miller

Dhanu’s office was a few blocks from Chuck’s, but they’d never met until a few years ago, when they bumped into each other while helping to campaign for the new UW Meat Science Laboratory. They got to know each other, and Chuck asked Dhanu whether he had ever heard of NF1. He hadn’t. Chuck told him about Mason, about the need for a better model, and about the promise that pigs offered to help understand and treat the disease. Then he asked Dhanu if he would join forces to help create that model.

Taking some time to think about it, Dhanu consulted the members of his laboratory who would all be helping to forge this new path. His risks would be their risks. A pig model could fail, leading them all down a blind alley.

Dhanu told Chuck he was in.

The risks remain significant, Dhanu says, “but I’ve come to terms with it, and it’s fine. I’ve been lucky in my career to work on things that have gone to clinic. If it works, it’s going to be impactful.”

There aren’t many places in the world where this kind of work — melding basic science with clinical research and a large animal model like swine — is possible. UW–Madison has large biomedical research centers, the capacity for high-powered basic science, and a 1,500-pig research facility called the Swine Research and Teaching Center (SRTC) in Arlington, a 35-minute drive from campus.

“It’s a brave new frontier, to move into swine,” says David H. Gutmann, a physician and researcher at the Washington University School of Medicine in St. Louis, who is considered one of the foremost NF1 experts in the world. “I’m glad they’re doing this work at UW–Madison because the combination of specialized resources and expertise are found in very few places worldwide.”

Like Scissors for Genes

Seen through a microscope, researcher Kathy Krentz guides a micro-needle to inject DNA into one of several pig embryos at UW–Madison’s Biotechnology Center. Photo by Jeff Miller

Dhanu and Chuck determined that the course they wanted to chart included gene editing using a powerful new tool known as CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats. The genetic technology is reshaping basic biological research. Like a pair of molecular scissors, CRISPR enables scientists to target a stretch of cellular DNA for alteration. They can cut out pieces of DNA or swap out letters in the genome, changing the message it encodes or shutting off genes entirely.

The two set their sights on creating pigs that carry the NF1 mutations they and other researchers are most interested in studying. “But we had to figure out where to start,” Dhanu says. “It’s like learning to fly a space shuttle.”

With Dhanu’s lab manager and lead scientist Jen Meudt at the helm, the team dove in. But the challenges were many. They had to learn about swine reproduction, about CRISPR and gene editing, how to perform the necessary surgeries on pigs, how to time events so no step of the process failed and ruined all the efforts before it. Again and again, they hit roadblocks.

It took more than a year, but finally, they came up with a plan: The researchers would use artificial insemination to impregnate a female pig carefully primed to produce more eggs than she naturally would. Shortly after fertilization, they would remove the embryos, whisk them to the Biotechnology Center, and inject them with a solution containing the gene-editing CRISPR. This would have to be done quickly, while the embryos were still a single cell. This way, when the single cell divided, all the subsequent cells would contain the NF1 mutation. (Inject too late and the pig would develop into a mosaic of cells that contain the mutation and those that do not.) Then it would be off to the surrogate mother, a pig chosen to reproductively match the embryo-donating pig. The researchers would perform surgery to implant the CRISPR embryos into her womb. If all went well, months later she would give birth to piglets, at least some of which would carry the desired NF1 mutations.

A few months passed. On Nov. 7, 2016, Chuck and Dhanu were meeting in Madison with a group from the Neurofibromatosis (NF) Network, which supports NF1 research and clinical care. They were sipping coffee when a text came in from Jen: “The mom carrying NF piglets is delivering right now.”

The piglets — eight in all, and four with the NF1 mutation — were a living embodiment of the team’s hard work. They had proved that they could create pigs genetically engineered to carry the disease. It was an emotional experience for the scientists, involving tears and prayers. They immediately went out to celebrate.

Then they set to work building on that success. One of the four piglets with the mutation is a male. Mason named him Tank. His job is to sire more piglets with the mutation since the changes conferred by CRISPR were designed to be passed on from generation to generation.

The team took the process they’d developed and applied it to other NF1 mutations, including some related to cancer. And they set an even more ambitious goal: precision medicine. In other words, a pig personalized for every child with NF1.

With CRISPR, the researchers believe they can take the genetic fingerprint of an individual child’s NF1 mutation and create a pig with that same mutation. They can then test potential medications and treatments and see if they’ll work. Can tumors, like the one that afflicts Mason, be shrunk?

The Promise of Precision

By the time Mason reached prekindergarten, the tumor in his face had grown into his cranial sinus. His parents were told he could lose his sight and his ability to taste. Surgery wasn’t an option. It was too risky and could leave Mason in even greater pain, permanently. “He’s literally been in pain his whole life,” Malia says.

Then, for reasons doctors couldn’t explain, the tumor stopped progressing. He regained his speech and no longer screamed or struggled to stay upright. His doctors keep a close watch on the tumor with MRI scans. They continue to work to determine the best medication regimen for the other symptoms that come with his particular variant of NF1. His treatment must be continuously modified.

Mason still exhibits some of the behavioral challenges often associated with NF1, which for him began at age 3. At age 5, he was diagnosed with autism. His parents say that, although it’s relatively late to get such a diagnosis, it opened up more therapeutic doors. Most doctors and insurance companies are unfamiliar with the social and behavioral implications of a NF1 diagnosis, but autism is well recognized and the need for early intervention well studied. Mason now sees an occupational therapist and speech-language pathologist in and out of school and a psychiatrist several times each year.

The therapy helps, but managing Mason’s disease has also taken a toll on the family. In 2016, with “everything fraying at the edges,” Malia says, the couple decided she would take time off from work to help refocus and slow down. She prepared to resign from her job working for a school district; instead, they offered her a one-year leave of absence. It provided the family the respite they needed, but it also presented a significant financial strain. “We laugh a lot because you have to,” Chuck says.

Alexandra and Mason Konsitzke play with their parents, Chuck and Malia Konsitzke, at the family’s home in Stoughton, Wis. To help the family face the challenges of living with NF1, Chuck says, “We laugh a lot, because you have to.” Photo by Jeff Miller

Laughter is just one way to cope with a disease with so many different faces. NF1’s unique manifestations make each child and each child’s treatment plan experiments unto themselves. But pigs develop faster than children do, so they offer the possibility of helping to predict how NF1 might affect a particular child, enabling parents, doctors, teachers, and others to prepare. Earlier intervention for a child who develops autism could lead to better outcomes. Doctors could start working to find drugs to treat tumors before they grow too large.

“Precision medicine is more than matching the right drug to the right gene. With NF1, it’s more complicated and involves searching for the factors that make each individual with NF1 unique,” says Washington University’s David Gutmann. “This is an amazing opportunity to find the risk factors that put an affected child at risk for developing a brain tumor, a bone defect, or another serious complication of NF1.”

Dhanu, Chuck, and Jen are not doing this work on their own. The team now includes many talented individuals like Biotechnology Center scientists C. Dustin Rubinstein, Kathy Krentz, and Michael Sussman, along with Jamie Reichert, manager of the Swine Research and Teaching Center, and his team. And there’s now a broader research group, the UW NF1 Translational Research team, which includes Thomas Crenshaw, an animal sciences professor and department chair, and Marc Wolman, a professor of integrative biology.

They have also enlisted the skill and knowledge of Neha Patel, a pediatrician at the UW–Madison School of Medicine and Public Health who treats about 150 children with NF1 in Wisconsin and surrounding regions.

Dhanu hopes to make the NF1 pigs accessible to other researchers around the country, charging only what it costs to produce them. And the team plans to use the pigs to help identify metabolic and cellular pathways common to the variety of NF1 mutations to help target and develop better drugs.

But to accomplish all of this requires funding.

“We’re at a critical moment,” Dhanu says. “We have to turn our successes into funding opportunities.”

The UW NF1 Translational Research team has bootstrapped most of its work so far, relying primarily on funding and donations from the NF Network. Most of that comes from an annual charity golf tournament the Konsitzkes and four other families help organize and run. Called Links for Lauren, the tournament honors Lauren Geier, an 8-year-old girl in Madison with NF1.

Finding funding for rare diseases through federal agencies like the National Institutes of Health can be challenging. However, families can play a surprisingly influential role in the fight against rare diseases.

“They often provide critical resources and financial support at the earliest stages of a highrisk project, when funding from federal agencies is not possible,” David Guttman says. “Our families, they inspire us because they ask us to do things that are really meaningful and take risks by taking the roads not frequently traveled. Through their involvement, they can move the field forward in ways that no one else can.”

‘Where There’s Research, There’s Hope’

Larry Britzman had no idea there were pigs at UW–Madison that might one day help children like his 12-year-old daughter, Mackenzie. He learned that, and much more, in May when he traveled to campus from La Valle, Wisconsin, for a symposium for NF1 patients and their families.

“I didn’t realize each child is specific,” he says. “I didn’t realize UW has swine research and there aren’t too many facilities in the country researching NF1.”

The NF1 team hopes to host the symposium each year, to invite families to learn more about the science of NF1, to give them a chance to meet researchers and clinicians, and to ask questions and meet other families living with the disease.

“We’ve gone very far in two years because it hasn’t been just about building a model, it’s also been about creating a community around it,” Dhanu says.

Larry Britzman and his 11-year old daughter, Mackenzie, who has NF1, talk to health advocate Lindsay Geier during the NF1 symposium. Photo by Jeff Miller

The opportunity to work so closely with and on behalf of the people who may ultimately benefit from his work is not something he’d ever experienced. And he has found it profoundly rewarding.

Not long ago, he invited a family into his lab whose college-aged daughter has NF1. They’d been donors to NF1 causes for years but had never talked to a researcher. “It meant a lot to them, and my first thought was: ‘How can we do more of this?’”

He and his lab members now participate in running events like the Madison Half Marathon, often with the NF Team organization, to raise money for NF1 research and to increase awareness. The runners sport neon yellow performance shirts with bold, black lettering. They also participate in the annual charity golf tournament.

“As scientists, we don’t often see the payoff of what we’re working on,” Dhanu says. “It redefines our research priorities, and it also aids discovery. The best people to note observations are the people who live with it.”

To him, success can be measured by individuals. “Even if our research just raises awareness and someone gets treated because of what we do, that alone is big,” he says.

Chuck believes the disease is underdiagnosed because very few people are genetically tested for it, and most physicians are not familiar with it. So they may diagnose patients with autism or a behavioral disorder and miss the broader picture.

That has frustrated Danielle Wood, a teacher and mother of two who lives in Reedsburg, Wisconsin. Her daughter, Bernadette, is 2 and was diagnosed with NF1 as an infant. Along with springy blonde curls and an arresting smile, Bernadette has a weak abdominal wall, which causes her pain and may require surgery. She wears braces to support her frail ankles.

Danielle, too, has NF1. Her mother had it and so did her grandmother. Though her condition is mild — she simply wears glasses for poor vision caused by a tumor on her optic nerve — deciding whether to have children was hard. Because it is a dominant mutation, Danielle and her husband had at least a 50 percent chance of giving birth to a baby with the disease. Having grown up with NF1, Danielle felt she had a good idea of what to expect. She now sees herself as an advocate for Bernadette.

“While things never move as fast as we want them to, there’s a tremendous amount of exciting progress in this field, and where there’s research, there’s hope,” David Gutmann says. UW–Madison is “in a really great position because (it has) young faculty who are excited and a patient community that is challenging them to improve the lives of people with NF1 through research.”

This is what drives Chuck, Dhanu, and the rest of the UW NF1 Translational Research team, which is working to establish a NF1 Center for Excellence at UW–Madison. Not only is this possible, David says, it is necessary. “There is no established therapy for NF1 and no magic bullet that works for all kids or adults. The challenge for us is to learn more about this disorder so that personalized and effective treatments emerge.”

Moreover, he says, what NF1 teaches researchers will inform their approaches to other conditions, like some types of cancer. And he’s excited to see what the future holds.

“All of us in the NF field get up every morning and are excited to get to work. What we learn from our colleagues and our families each day brings us one step closer to that better future for children and adults with NF,” he says. “I can imagine getting up every morning and running to work to see what’s happening with those pigs.”

For Mason, pigs — including Tank — don’t play much of a role in his daily life today. Instead, he continues regular visits to therapists and other professionals to help him manage his symptoms. He also benefits from the support of his family, from Chuck and Malia to aunts and uncles who have learned all they can about NF1. And the family dog, Donatella, is his packmate, Malia says. But at 7, Mason can still take all of that for granted and focus on what he loves best. Like sharing the tastiest mini pizzas he can make. He would absolutely love it if you tried one.

The Method Maker

Gerry Weiss BS’67 admits he knew nothing about the steep-valleyed fields of southwestern Wisconsin when, back in 1975, he bought 350 acres in Grant County and started raising forage, row crops, swine, and beef cattle. A native of flatter lands in Dane and Columbia counties, he knew the unfamiliar geography would present a true challenge, perhaps decades of trial and error. But Weiss began farmwork at age five, and he was taught to appreciate an experimental attitude right from the start.

“My father and my two uncles were innovators,” says Weiss, now 72, as we sit at his kitchen table, stacked high with papers, research studies, and farm magazines. “I learned that you advance by being more efficient, more focused. They told me, ‘The answers are in front of you. Keep your eyes open.’”

Following their advice helped him earn agricultural accolades at an early age. He reveals to me that he is still the only FFA member to be named State Star Farmer, State FFA Speaking Contest winner, and State FFA Officer all in one year. That prodigious resume, combined with his incisive nature, propelled him to earn a B.S. (with honors) in animal sciences at CALS and a doctorate from Iowa State University, though he occasionally mocks his Ph.D. as standing for “piled higher and deeper.”

Weiss is intelligent, erudite, and challenging, with an unpredictable, probing sense of humor and a proclivity to pun in English and German — a vestige of his time as a postdoctoral researcher in the Netherlands and Germany in the 1970s. He followed his work abroad with a stint as senior meat scientist at Union Carbide and then a job as assistant to the president, focused on technology and science integration, at Dubuque Packing Company

His education and private sector career did not, however, teach Weiss much about permaculture, rotational grazing, humane ways to wean cattle, or a hundred other systems, tactics, and processes that he invented, honed, or proved on his land and in his barns. Thinking of these innovations, I suggest to Weiss that he seems to have carved his own furrow, but he balks at my words. “I have not plowed a single furrow in Grant County,” he says.

What he means is that, in 40 years of farming, he has not used a moldboard plow — the device that John Deere invented in 1837 and is still used today. By turning over the soil and exposing it to rain and wind, the moldboard plow raises conservation questions, at least to a visionary like Weiss.

The seven pastures on Weiss’ terraced farmland converge at this point to promote the easy movement of his herd of Gelbvieh cows. “After five days of grazing in one pasture, they come here to let me know they’re ready to move,” he says. “All you have to do is swing a gate. No trap pens, no catching cattle, no hauling them to the next pasture.” The use of this system of rotational grazing in Wisconsin was cultivated by Richard Vatthauer, an emeritus professor of animal sciences, and Bill Paulson, former superintendent at UW’s Lancaster research station, Weiss says. Rotational grazing keeps weeds in check while stimulating grass growth, which helps prevent soil erosion. Photo by Mark Hirsch

‘We Attitude’

Weiss’s sloping farm, located just a few miles from UW–Madison’s Lancaster Agricultural Research Station, sits inside Wisconsin’s Driftless Area. The region is known for its exceptionally rugged terrain due to the utter lack of glacial bulldozing (i.e., drift) and for the meandering paths that the Wisconsin and Mississippi rivers and their tributaries have slashed through the landscape.

Many Wisconsinites look upon this unique geography — and the adaptations necessary for living within it — with genuine pride. Likewise, many are proud of the connections between CALS and the economic engines of farming and food processing. These linked industries are vital to the state; they employ 413,500 people and generate $88.3 billion in economic activity.

Weiss resides at the heart of all of this — a born innovator who adjusts to the conditions thrust upon him and exemplifies the connection between academic experts and those who make a living raising crops and animals. And it’s a pipeline that flows in both directions. Weiss credits Bill Paulson, former superintendent at the Lancaster station, with valuable suggestions for weed control and a seed mix for improved pastures and other conservation practices, such as waterways, that still thrive today. It was the first of many connections that have benefited Weiss — and CALS — over the course of four decades.

Some of this collaboration pertains to permaculture, that basket of approaches to farming that develops sustainable agricultural ecosystems through thoughtful observation and creativity. Despite the name, permaculture is not, Weiss says, a “set-and-forget” operation. It takes real work to manage acres of permanent pasture. Fortunately, Weiss is energetic — and relentless.

“I have never worked with terraces that have had so much constant maintenance,” says Grant County soil conservationist Kevin Lange, who has worked with Weiss for almost 30 years. “He’ll fix the rodent holes, scrape the soil back to the top.”

Weiss does all of this in addition to testing the soil, fertilizing as needed, winning the war on weeds, and conducting his own research. The last one, according to Lange, is special — most farmers lack the time for it. “If they are interested in research, they are interested in reading somebody else’s work,” he says. “He’s always checking in, always got something new he wants to try.”

Any success he’s had, Weiss attributes to what he calls a “we attitude,” a propensity for collaboration. This mentality has led to fruitful partnerships with two land-grant institutions (UW– Madison and Iowa State University) and their associated extension units and agricultural research stations, as well as the Natural Resources Conservation Service (NRCS) at the U.S. Department of Agriculture. “I don’t know all of the answers,” he says. “And if I don’t know it, I’m on the phone, and I’ll admit that I don’t know it.”

To find the answers, Weiss asks some tough questions. Lange admits that he can be an acquired taste. “Sometimes when he calls, you have to take a certain amount of his guff and give back a little bit of lip of your own,” he says. “But it’s not too insulting. That’s just our thing. Somehow, I got to be his guy.”

 ‘The Animals Taught Us’

Weiss’s agricultural education, and his unusual approaches to the hurdles of farm life, began with his father’s wisdom about “open eyes.” One outcome of that observant nature appears as soon as we enter Weiss’s cattle housing. At first, I wonder whether I’m in a barn or a carnival fun house lightly scented with manure. The floor is nowhere close to level, the gates are built to telescope to different lengths, and odd angles are as common as right ones.

These peculiar features are all designed to get cattle to move where he wants, Weiss says, and they’re built to suit the innate tendencies of a herd. “The animals taught us,” he says. “They like to stick together, to walk along the wall, and to walk downhill. We don’t use sticks or prods to move them. Don’t need to.”

The highway guardrails outside the barn also represent lessons learned from the cattle. They’re part of a humane, common-sense system that started with fence-line weaning, the practice of allowing cows and their young to associate — but not nurse — to ease a traumatic separation. The technique presented itself as the solution to an obvious need if your eyes — and ears — were open, Weiss says.

After weaning, “You could look at the anxiety of the calf and its mother and could tell it was pretty high,” he says. “The calf would stand in the gate area, bellering until it lost its voice, and the cow would stand at the pasture gate somewhere and beller. Nobody was happy. You could bring a baton and direct the orchestra.”

But the whole equation changes if the pair can see, smell, and even touch each other. “They have less stress,” Weiss says. “Baby can talk to its mother, and she can look through the fence [or guardrail] and see that her baby’s okay.” Within days, both sides have quit singing the separation blues.

Decades later, fence-line weaning is gaining acceptance in beef operations. The benefits, Weiss says, are measurable. “We weigh when we wean and again before we sell the calves as feeders. They are gaining 1.8 or 2 pounds per head per day. With high-stress weaning, they are pacing, bellering. They’re pretty woundup little critters, and the gain is more like 0.75 or 1 pound per head per day.”

Defying conventional weaning wisdom led to another example of the “Weiss method,” one designed to address what he calls “another part of the horrible tradition” with calf weaning. “You would jab them with needles for antibiotics and vaccine,” Weiss says. “Talk about making a calf feel great! It would take four to six weeks to get past all that.”

That was the way it had always been done. But Weiss had better ideas, many of them related to vaccinations. In the late 1970s, he helped Norden Labs of Lincoln, Nebraska, demonstrate a protocol designed to prevent E. coli infection and rotavirus in calves, a method that involves no stressful catching or needle pricking. “We administered this to the beef cows two weeks prepartum to generate maternal antibodies for the mom to pass on to the newborn calf,” Weiss says. “Our calf scour [diarrhea] incidence dropped to zero and has remained at zero since our working with this vaccine.”

“That vaccine … which originally goes back to the Norden product, is one of the most, if not the most, commonly used methods to prevent E. coli and rotavirus diarrhea in calves,” says Simon Peek, a clinical professor of large animal internal medicine at the UW–Madison School of Veterinary Medicine. “It’s something pertinent, relevant to the state, and it’s definitely made a big contribution.”

 ‘We Developed Biosecurity Before It Was a Word’

To Weiss, continuous improvement is simply common sense. “You make advances step by step,” he says. “We saw the same attitude at CALS and at Iowa State. Once you do something, you see an opportunity to do it even better.”

He learned this method early through his father and uncles, who were early adopters of farrowing crates for swine. “Originally there was a 5-foot by 7-foot pen, but we transformed that to put mother in a more confined area so it would be harder to lay on her little ones,” he says. “Then we hung a heat lamp to draw them away from mother. Then we raised the farrowing crate to keep the young pigs off the cold concrete floor, and manure would fall through the grate so the babies stayed clean.”

Demonstrating the ingenuity that has helped drive Wisconsin to the forefront of animal agriculture, the Weiss farmers developed a system that involves washing the sows to remove worm eggs and manure and then washing the crates as well. “A clean mom with a clean udder is a whole lot better than a dirty mom,” Weiss says. “We progressed to a much-improved, higher-growth performance with a much lower load of bacteria and worms. We helped develop biosecurity before it was a word.”

Weiss found other ways to focus his creativity on animals. In 1994, he built a specialized pig barn designed for scientific investigation. As proprietor of the on-farm science business Progress Plus LLC, Weiss has used the barn to perform contract research for the late Mark Cook, professor of animal sciences, as well as private firms in the hog industry. The building has five rooms, each with its own feed supply and manure pit, to enable side-by-side comparisons of input and output in swine.

“There are so many variables, so this barn was ideal for conducting complex trials quickly,” Weiss says.

It’s also the perfect place for a data-obsessed farmer-scientist, one who listens to an inner voice and never settles for “good” when “great” is begging to be invented.

The entrance and exit to special swine housing on Gerry Weiss’ farm sits at trailer height for ease of loading and unloading pigs. The ramp has shallow steps that are easier for animals to navigate and makes a 45-degree turn so pigs are urged on by their own curiosity rather than being driven. “They want to know what’s around the corner,” Weiss says. “I have never carried a weaned pig up that ramp.” The system, which he says he borrowed from Madison’s Oscar Mayer plant where he made swine deliveries in his youth, reduces stress for pigs and hassle for farmers and processors.   Photo by Mark Hirsch

‘I Didn’t Know Anything about This Stuff’

As we cruise Weiss’ farm on a tractor road, I notice the ride is exceptionally smooth — no ruts, wallows, or washouts. So he tells me about the 10-inch layer of breaker run and gravel beneath his pickup. The overkill design is not needed on this dry summer day, but when he has to tend the cattle or haul manure in the rain, it prevents wheels churning through the mud, which would translate into erosion.

Even after July’s staggering rainfall, there’s no mud, no hint of a gully, no erosion in sight throughout our drive.

The subject of erosion returns us to the 1970s and to the role of publicly supported science. “I grew up on the Arlington prairie,” Weiss says. “I didn’t know anything about this stuff out here.” From the USDA NRCS, he received advice on filling gullies and constructing terraces, diversions, and waterways to halt soil erosion that had measured 13.1 tons per acre per year on his land. Some of those gullies, he says, were deep enough to hide the bulldozer that he hired to repair them.

A despiser of waste, Weiss was loath to take the waterways out of production, and he figured hay or conservation practices would yield a saleable crop while preventing erosion. And so, unembarrassed by his ignorance, he contacted Bill Paulson, then the superintendent of UW–Madison’s nearby Lancaster experimental station.

“USDA had its own seeding specifications,” Weiss says, “but the difference was that Bill had actually done it. He’d perfected the seed mixture; it was an unbelievably positive addition to what we were doing. Bill knew what would work here.”

Thirty-eight years later, Weiss continues to do soil tests and fertilize as needed, but he has not had to reseed his pasture. “We just take the hay off,” he says. When waterways and terraces are always covered, soil and stream bank erosion are practically zero.

“It may seem obvious, but I’ve never had anybody mention [hay harvest from waterways] to me,” says Dan Schaefer BS’73 MS’75, longtime head of the Department of Animal Sciences, when asked about Weiss’ permanent seeding of these erosion protections. Meanwhile, Weiss is happily hauling hay, which is profitable in today’s market.

This initial interaction with Paulson led to many more collaborations with CALS. Weiss has opened his own land and crops for pesticide trials conducted by the departments of agronomy and entomology. Last summer, the only row crop on the farm was a soybean trial that assessed weed resistance to herbicide. All in all, Weiss has taken part in more than 220 research trials related to animals and crops.

‘People Thought I Was Nuts’

Decades ago, the process of accounting for homegrown organic fertilizer became another element of the Weiss method. Working with UW researchers, he developed systems to track the nitrogen and phosphorus added to the soil by manure and legume crops.

“I was one of the first to utilize manure in a nutrient management plan, working with [Grant County] UW Cooperative Extension agent Ted Bay MS’80,” Weiss says. In two growing seasons, using soil analyses from the Marshfield Agricultural Research Station, he cut his fertilizer bill by 70 percent. As with his work with cattle, one improvement begat another. To maximize savings, Weiss bought a manure spreader able to change application rates to supplement nutrients based on variations in soil tests.

But the simple logic in favor of buying only as much fertilizer as you need would have been plowed under had Weiss listened to his neighbors — or his fertilizer dealer. “People thought I was nuts, yes, for 25, 30 years,” Weiss says, “but we were supported by the agronomy and soil science faculty in Madison.”

If you spend enough time with Weiss, you begin to assume that any allusion to conventional wisdom will be chucked to the wayside if not squarely onto the dung heap of history. It’s how he stays ahead of the curve. Today, the “nutrient credits” that can reduce fertilizer use and environmental damage are required on many Wisconsin farms. They’re also integral to SnapPlus, a software program created by experts at the Department of Soil Science.

“SnapPlus solves several problems at once, related to distributing manure and fertilizer efficiently, while meeting guidelines for protecting groundwater and surface water,” says associate scientist Laura Good MS’88 PhD’02, who has led its development and testing. “The program helps to maintain crop fertility without wasting money or endangering natural resources.”

Just like manure, legumes are a critical part of permaculture. Aided by soil microbes, plants like alfalfa and clover absorb nitrogen from the atmosphere and put it back in the soil to make it more fertile. Decades ago, when most farmers dedicated fields to pasture or row crops, Weiss planted legumes in his permanent pastures and pioneered the use of “rotational grazing.” Moving cattle from field to field not only protects the pasture from trampling and overgrazing but also reduces tilling and hauling of feed and manure. At the same time, it increases fertility and productivity, so any given field can support more animals. The practice of moving cattle is now a mainstay of organic and other low-impact agriculture.

Gerry Weiss surveys his farm from the seat of his pick-up truck while parked at a high point in one of the pastures. Photo by Mark Hirsch

‘You Don’t Need to Do This!’

Weiss’s collaborations with CALS have also involved planting innovations. At a time when planting and cultivating corn entailed at least a half-dozen passes across the field, he teamed up with frequent collaborator Paulson, soil science professor Larry Bundy, and agronomy professor Ron Doersch BS’58 MS’61 PhD’63 to develop a two-pass corn-planting system.

“You disk in manure and cornstalk residue with a heavy disk, doing primary tilling in one pass,” he says. Then, aggressive trash whippers on the planter clear a seven-inch row for the corn as the planter sprays a preemergent herbicide.

“We found that most years, with normal rain, we got such tremendous activity from the preemergent herbicide that we did not need a second pass of spraying, but a very limited number of people have picked that up,” Weiss says. “They are locked into four to seven passes for tilling, planting, spraying, and then spraying again. People, you don’t need to do this! We are reducing labor, soil compaction, and fuel burn, and also recreational tillage.”

But having a motive to disbelieve can overpower the evidence of open eyes, he adds. “I’ve had salesperson after salesperson come here to look at a field after the soybeans have been drilled and shake their heads,” Weiss says. “The field is still relatively rough, which I want for rain erosion prevention. I’ve had many of these guys come back at harvest, and say, ‘This is really a tremendous plant environment.’ When I respond, ‘But four months ago, you told me this was a disaster,’ they get real quiet. But it always seems easier to criticize than to try to understand why I keep doing it.”

A different attitude, both positive and more open-minded, prevails at UW–Madison and the other land-grant institutions, Weiss says, and the attitude is mutual. “He has always been respectful of faculty, though he will speak out if someone has a loony idea,” Schaefer says. “He’s principled, all about accurate data, accurate communication. There’s no varnishing, no window dressing. ‘Tell it to me the way it is.’”

In this way, Weiss has managed to survive in the ever-changing farm economy for 40 years. Today growing forage is profitable, so hay is what he sells, usually delivered to horse owners in small bales.

The swine barn is now empty — another victim of harsh market conditions — so the Gelbvieh cows that Weiss collaborated to import from Germany in the 1970s are his only livestock. Having grown to understand (so I think) the many labor-saving and cow saving innovations on the farm, I ask why he has only 60 head. As the question hovers above the kitchen table, I immediately realize that I have plunged into the manure pit called conventional wisdom. Bigger is not necessarily better, and the answer is in front of my face, though Weiss is kind enough not to mention that.

“I match the cow herd to the rotational grazed pasture program,” he says. “Sixty head is my carrying capacity with my current 68 acres of permanent pasture, but we have plenty of room for more pasture here.”

Such an expansion, Weiss says, would best be carried out by the next generation of stewards of his land. He is now on the hunt for a “very special person or people” to continue where he leaves off. When students of the agricultural sciences visit his farm to learn from its innovations, he tells them his successor just might be among their ranks.

“I also tell them,” Weiss says, “that I haven’t made all of the mistakes yet, but I’m getting close.”

‘The Barbs Are Quite Dull; They Are Just Gerry Weiss’

Thinking back, Weiss’ meticulous attention to the land and his characteristic dry wit are both on display the moment we first meet. I drive onto the farmstead with my road bike racked behind my economy Honda and approach a weathered, white-haired guy pitchforking Canada thistles from the back of a white Ford pickup.

By way of introduction, I ask, “Aren’t you too old for that?” He responds, “Oh, I think we’re going to get along just fine. You can give it back.”

Later that day, as we tour the fields, I tease Weiss about a lone Canada thistle proudly blossoming above a pasture. Even a city fellow knows that those splendid purple flowers are one of Wisconsin’s premier pasture pests, and Weiss immediately promises to annihilate it to block it from reseeding.

I mention the thistle to Lange, the Grant County conservationist, and he remarks, “I’m surprised that he did not write down the location. If he was younger, he would have put it on GPS, but I’m sure it’s gone by now.” Indeed, when Weiss later meets me for lunch in Spring Green, he hands me a thorny, withered thistle. “Some salad from the farm!” he says.

“He’s very conservation conscious,” says weed expert Jerry Doll, professor emeritus of agronomy. “He once called after an 8-inch rain, happy that his grass waterways and terraces had no visible erosion, while his neighbors were looking at gullies.”

“His mind is always churning,” Doll adds. “I don’t know how he sleeps at night. I know his power of observation. When he sees something he can’t explain, he’s on the phone.”

Like Doll, others who have worked with Weiss typically cite his inquiring mind and diligence, as well as his devotion to conservation. They also like to mention his low-grade combative nature.

“Gerry is very bright and quite self-deprecating,” Schaefer says. “He can be prickly and takes pride in barbed comments, but he does that mostly for effect. He wants to know if he’s getting through to you. The barbs are quite dull; they are just Gerry Weiss.”

But underneath Weiss’ thorny exterior, Schaefer sees the embodiment of a precept of the great Midwestern public universities. “He’s a land-grant creation. To me, he epitomizes the application of science to agriculture.”

Gut Dwellers

Fermentation Fest

Fermentation Fest, sponsored by the Wormfarm Institute, is an annual celebration of “live culture” held in Sauk County. These scenes are from the 2017 fest, where Federico Rey gave a presentation on the human gut microbiome. Photos by Katrin Talbot MS’85

The second floor gallery of the Wormfarm Institute in Reedsburg, Wisconsin, is a far cry from the funky glassware and biosafety protocols of a working microbiology lab. One corner contains an improv kitchenette, circa 1987. Sprout — the mascot offspring of the Jolly Green Giant — waves improbably from behind a cubicle wall across the room; the child-size plastic statue is missing a hand. A cool draft of autumn rain and small-town traffic noise flows through an open window.

Assistant professor of bacteriology Federico Rey chats with his Wormfarm hosts as more than three dozen attendees of the annual Fermentation Fest assemble into a casual arc of folding chairs and a couple of vintage couches. These are people who already understand the idea of microbes as friends. Makers of coleslaw and kimchi, kombucha and beer — they are motivated by microbes and have paid to hear Rey’s summary of the state of current human microbiome research.

Across the life sciences, the microbiome is the buzziest of buzzwords, invoking a symphony of hope, hyperbole, and high expectations. Rey shares in the overall enthusiasm, but he is careful about the speculative details. Yes, the microbiome might even match our frothiest expectations. And no, he can’t cure your diabetes or make you leaner, faster, or smarter. He can’t even tell you if your microbiome is healthy. Not today.

Because nobody can.

In front of a large wall hanging of textile orange circles representing the bubbles of fermentation, he begins where he has to begin, very near the beginning. “Microbes are the most abundant form of life on this planet,” he says, his thick Argentinian accent backlit by a docent’s enthusiasm. “They can live in places where we cannot imagine life.”

“Microbes outnumber us by many orders of magnitude. They power almost everything on the earth,” he says. They convert as much carbon dioxide into organic compounds as plants do and emit more methane than the oil and gas industry. “Literally, there is no place on earth where there are no microbes,” he continues.”It is impossible to get rid of them.” And despite our germophobia, they’re mostly good company: “A very small fraction of microbes are pathogens. Most of them are commensal — they don’t do good or bad — or they are beneficial for humans.” These last ones, the microbes that fuel our fantasies of easy cures and everlasting health, truly capture Rey’s interest.

Every surface on our bodies is colonized by some kind of microbe, and microbiologists have identified thousands of species of bacteria that can inhabit the human gut. Each of us, in turn, has a collection of between 100 and 200 different bacteria strains, comingled with other life forms from fungi and protists to viruses and archaea. These enteric ecosystems — different for every single human, even more unique than a fingerprint — each contain 100 times the genetic information of our own cells. They both supplement and interact with our bodily blueprints.

Deciphering who’s who is not even half the problem. How exactly do our bodies gather these microbes? What shapes the resulting ecosystem? How do humans and microbes interact? In 2017 alone, Rey published new research about microbiome effects in diabetes, Alzheimer’s, and the cycling of the nutrient choline (which may positively affect fetal brain development but also can lead to heart disease later). “Every single disease or health condition scientists look at, they find a microbiome connection,” he says.

And yet there is no single definition of a healthy microbiota. And what is healthy for you may not be healthy for me.

Research Revolution

Federico Rey arrived in the United States in 1999 with advanced biological questions on his mind and little idea that microbes could hold the answer. As a research fellow at the Henry Ford Health Sciences Center in Detroit, he focused on hypertension and vascular disease. But when he moved to the University of Iowa for his Ph.D. in 2001, he met Rhodopseudomonas palustris during a lab rotation. These extravagantly versatile bacteria are known for their ability to use four different modes of metabolism to scavenge energy, nitrogen, and carbon from a variety of sources — with or without oxygen. Intrigued by the diversity and adaptability of microbes, Rey says he fell in love with the bacterium.

R. palustris was an obvious stepping-stone towards biofuels. But in 2005, Rey saw a talk by Jeff Gordon, a pioneer in the study of human-microbiome interactions. Gordon began examining the development of the mammalian gut in the 1980s. Eventually he realized that microbes were essential to the process, and he set out to untangle this complex relationship using early sequencing techniques and transgenic and germ-free mice.

Rey joined Gordon’s lab at Washington University in St. Louis as a postdoc in 2006 just as microbiome science was gaining momentum. Tools for reading the genetic code were getting faster, cheaper, and more versatile. Computers used to crunch burgeoning data sets were growing in power as new statistical methods were increasing in sophistication.

One of the earliest hints of the power of microbes was that transplanting the microbiome from one mouse to another could also transfer basic metabolic conditions, such as obesity. It was in Gordon’s lab that Rey first met CALS professor of biochemistry Alan Attie — through the microbes of his mice. In Attie’s efforts to unravel the many mysteries of diabetes, his lab sent Gordon microbiome samples from genetically distinct mice that had been placed on a high-fat or a chow (i.e., grain-based) diet. It was known that both diet and genetics had a significant effect on the metabolic health of these mice. Gordon helped to show that the microbes played a role as well.

Rey took the project with him when he was hired by CALS in 2013, and he’s been collaborating with Attie since. It’s a task of daunting complexity: integrate two genetically complex systems that play a role in metabolic disease. Neither is close to being perfectly understood, yet they interact with each other, coalescing in each individual.

Hundreds of mammalian genes are already understood as part of the metabolic pathways that go awry on the way to diabetes. The human microbiome, meanwhile, produces thousands of chemicals that act within the genetic framework of humans. We’ve long understood how these microbes help us break down the complex compounds in the plant-based foods we eat, providing about 10 percent more energy. More recently, we’ve learned how these microbial bioreactors produce molecules called short-chain fatty acids — acetic acid, propionic acid, butyrate, and other products of fermentation that signal our bodies in health-promoting ways.

Our bodies sense these molecules, helping regulate things like gastrointestinal motility. Less well understood are the thousands of chemicals that train our immune system and help regulate everything from kidney function to brain chemistry.

“This is one of the most important aspects of the microbiome that is revolutionizing biology,” Rey says. But unraveling the interplay between host genetics and metabolism is anything but easy.

Julia Kreznar inspects a germ-free mouse while performing cage maintenance. Sterile germ-free mouse facilities on the UW– Madison campus provide a controlled model in which to study the interactions of microbial communities within mammals and how they impact anatomy, physiology, behavior, and susceptibility to disease. Photo by Michael P. King

In the Rey lab, senior scientist Bob Kerby holds two sealed test tubes (left) containing a pure strain of bacterium from a human fecal sample. The cloudy sample has been incubated for 24 hours; the clear sample has just been prepared. The Petri dish holds the bacterial colony. Photos by Michael P. King

In work published in Cell Reports in 2017, Rey’s student Julia Kreznar used eight different mouse strains and microbial transplants to help unravel this tangled web. The study found measurable differences in the microbiome established in the different strains. These microbes, in turn, influenced the likelihood that the mice would succumb to metabolic disease. The work also demonstrated a novel link between the gut microbiome and insulin secretion.

“We can show that microbiota affected pancreatic islet physiology and function,” Kreznar says. It’s a promising step, but it’s also an indirect interaction. Identifying the mediators of these microbe-host interactions is really challenging.

“It’s the dawn of a new field,” Attie says. “We have 3 or 4 pounds of organisms that are producing so many molecules, and we don’t know the least of them.”

“I’m feeling daunted,” he admits. “We had this idea that we would potentially connect the dots genetically. It is enormously complex, and it’s hard. It’s harder than we even thought it was going to be.”

A Big Genetic Black Box

Back in Reedsburg, Rey knows the probiotic question is coming, so he makes a preemptive strike: “When I talk about microbiota, I’m not talking about probiotics. The probiotics that you can get at Walgreens are basically microbes from dairy, microbes that can live in milk. Microbes that are not adapted to live in our intestines.”

If the microbiome has taught him anything, it’s that generalizations are tricky. “If they work for you, you should continue,” he emphasizes, trying to claim middle ground. Because of course, probiotics are microbes, and there actually is a lot of evidence that some may provide immune benefits.

But you won’t get a better microbiota by eating probiotics, and if you don’t eat your yogurt on Saturday, by Sunday those yogurt microbes are pretty much gone. They just pass through. “The effect is good as long as you keep eating them. And that is the perfect model for a company, right?” he says, with a tone of innocent mischief.

But if you look at probiotics through the lens of the microbiota, you have to acknowledge this essential truth: It’s been a landmark decade, but we still don’t have tools that are sophisticated enough to measure the microbiota in sufficient detail. We still don’t have an adequate biological understanding of what makes a healthy microbiota. And we barely understand the complex dance these microbes do with our body. Add in the fact that probiotics are dietary supplements, and thus not well regulated.

“You have to be careful. You have to do your research,” Rey says. “There are many different strains of probiotics, and there are big differences between different strains.” This is further complicated by the difficulty of even properly identifying bacteria, which can evolve rapidly. “There is a big difference between George Clooney the actor and somebody named George Clooney who lives in Atlanta. They have the same name, but they are completely different people,” he explains. “There are thousands of strains of Lactobacillus rhamnosus. Some may have an effect. Many of them probably don’t.”

In fact, it is our ability to identify these subtle differences in microbes that sparked the current revolution in microbiome science. First came 16S ribosomal RNA. Essential to the construction of proteins, 16S changes very slowly, which allowed scientists to, finally, reliably identify the members in a microbial community.

We talk about DNA as the book of life. At first, just reading a few pages was a chore. Then we developed machines to read more pages, faster. Then we learned how to read the sequels: DNA makes RNA, which makes proteins and enzymes responsible for carrying out cellular processes, including the making and breaking of sugar for energy. The technology responsible for reading these interrelated genetic codes is called next-generation sequencing, and it has powered this first golden age of microbiome research. The challenge now is sifting through that data to find biological meaning. Postdoc Lindsay Traeger PhD’15 is one of Rey’s primary number crunchers. “I’m attracted to very broad questions that we can throw a data hammer at and see what falls out,” she says.

Right now Traeger is focused on the next stage of collaboration with Attie and several other UW–Madison faculty including Joshua Coon (biomolecular chemistry), Karl Broman (biostatistics and medical informatics), and Brian Yandell (statistics). “We know that the gut microbiome is influenced by diet,” Traeger says. “But there is also this genetic component, which is a black box.”

Using genetically distinct mouse strains is advantageous when you’re trying to model a particular disease. But if you’re trying to tease out broader biological principles, using a single strain of mice could lead to bias. That’s why the labs are using a special breed called Diversity Outbred, a strategic genetic mash-up of common lab strains and some wild strains.

In one hand, Traeger has the genetic code of each individual mouse. And in the other, she has the genetic code of the microbiome of each mouse. Using advanced statistics, she’s searching for patterns that suggest some molecular matchmaking.

A germ-free mouse in its sterile quarters on the UW–Madison campus. Photo by Michael P. King

“I’m trying to identify how the host is selecting for or deselecting for the presence and abundance of certain microbial functions. Because the microbes are interacting somehow with the host.” One gene of interest is responsible for creating the important immune protein TNF-alpha, which plays roles in cancer and autoimmune disease. Early returns suggest that the TNF gene is also involved in sensing and responding to bacteria that have flagella.

Of course, the TNF gene is only one of about 23,000 genes, while the genes associated with bacterial flagella are just a few out of potentially hundreds of thousands. With numbers that big, there’s a lot of noise to filter out. And lots of distractions. “It’s a little hard to focus,” she laughs. “I think I could just spiral off. [Rey] keeps me thinking about the biology.” Rey’s endless creative energy helps. “He’ll just bust into the office and say, ‘I have this idea!’”

The immensity of the black box also keeps the work exciting. “We do think we’re going to find some interesting examples of interaction of host and microbiome,” she says.

Two T-Bones a Day

The microbiome is a dynamic force. Change the diets of lab mice, and overnight the communities that live in their gut change dramatically. So why care what microbes are in your gut if you can switch it up that quickly?

Rey points to his classic Argentinian upbringing as an example. “I grew up eating a T-bone for lunch and a T-bone for dinner,” he says. “Twenty-five years. And I miss it very much,” he quips, evoking another laugh from his audience. “But if I became vegetarian long term, I would definitely select for different microbial communities. And I would likely have new microbes colonize me.”

But even while your gut community is adaptable, the microbes in your gut can also have long-term consequences. That T-bone? “There are components in meat that microbes love and that cause problems,” Rey warns. “But you might not have them.” Which could mean several things: You’ve never been exposed to them, or you’ve been exposed but they didn’t take. Or maybe they’re there, but other microbes keep them in check. All of those are open biological questions, which now makes nutrition even more complicated.

In 2011, Stanley Hazen of the Cleveland Clinic published a paper linking microbes to the breakdown of lipid phosphatidylcholine (lecithin) into several choline-related compounds, particularly TMAO (trimethylamine N-oxide), a chemical already found to be a strong predictor of heart disease risk. Specifically, microbes metabolized choline into trimethylamine (TMA), which is then converted in the liver to TMAO.

While diet is a big part of this risk — eggs, milk, liver, red meat, poultry, shellfish, and fish are major dietary sources — the combination of microbial and host biology leading to TMAO accumulation intrigued Kymberleigh Romano PhD’17, who decided to dig deeper for her doctoral work with Rey and was co-mentored by Daniel AmadorNoguez, an assistant professor in bacteriology with expertise in metabolomics. Despite years of lab experience, she’d never worked with lab animals before, but she knew the time had come. “A lot of the phenotypes we study exist only in the context of a host-microbe interaction,” she says. “A test tube is never going to develop heart disease.”

First she needed microbes. Harvard researcher Emily Balskus had identified the genes involved in microbial conversion of choline to TMA, and Romano began looking for them in human-associated microbes and constructing experimental mixes of microbes. As she tinkered she found that, in mice at least, you need a TMA producer present in the intestinal microbiota to see TMA accumulation. And as you add more TMA-producing species, less choline is left for the host.

Even though she’d narrowed down the difference to a single organism in her custom microbiota, it still wasn’t enough. One bacterium contains anywhere from 3,000 to 5,000 genes — that’s a lot of variables. Fortunately, her collaborator from Harvard had identified a genetically tractable choline consumer and knocked out the TMA production gene. “Now the only difference in my communities was a single gene.”

Cardiovascular risk aside, choline is an underappreciated nutrient contributing to the process of epigenetic regulation of gene expression, and those without enough of it are more likely to suffer metabolic disease. In mice and rats, there is even a two-day window during pregnancy where lack of choline can impact fetal brain development. “Biology is never simple,” says Romano. “If it’s simple, you’re missing something.”

Eat Your Vegetables

Talking about poop makes people laugh, and as Rey wraps up in Reedsburg, the crowd has stayed engaged, surviving even his brief foray into 16S sequencing.

His advice for microbial health is folksy and charming. “Spouses share more microbes than people that don’t live together,” Rey tells the crowd. “We have found that spouses who get along together share more microbes than spouses that don’t. There is a lot of exchange going on there.” (In fact, if you’ve had to take antibiotics, he suggests family time will do more to restore your microbes than probiotics.)

And, noting that the most diverse microbiomes are found in places like the Amazon, he says being exposed to dirt is probably a good thing. “Get your hands dirty working in your garden,” he says. “I think that’s a health habit that we have lost over the years.”

Still, stubborn ideas persist among those gathered in the room. About a dozen times people bring up their pet microbiome theories for validation: probiotics, kombucha, fermented food, raw food, red wine vinegar, minimal vegetable washing, fecal transplants.

“The microbiome has come to mean anything you want it to mean,” Rey says disarmingly, for another laugh.

But “I don’t know” is his most honest answer. It’s a conundrum: The microbiome is hot in part because of some stunning findings. Most remarkable is the use of fecal transplants to cure drug-resistant Clostridium difficile infections, with cure rates running above 90 percent in some studies.

That extraordinary outcome certainly got the attention of both the medical community and the fad diet community. And even as it validates the power of the microbiome, that outcome actually runs against the grain of all the variation Rey is trying to figure out. “My lab is very interested in understanding the consequences of our interpersonal differences,” he explains.

“I can sequence your microbes, and I would not be able to tell you what vegetables to eat,” he says. “Maybe in 5 or 10 years personalized nutrition will be a reality, but it is not today. The one recommendation we can give right now is try to think about feeding your microbes. Because we cannot tell you what will be the best for your microbiota.”

In other words, eat your vegetables. Let’s say you eat pizza, with regular flour dough and cheese. Your body can digest every single ingredient of that pizza. By the time it reaches your large intestine, where most of your microbes live, your body has absorbed everything of nutritional value.

“You’re not sharing any of your food with your microbes,” he explains. “That’s one of the things we are doing with our Westernized diets: we are starving our microbes.”

“Maybe broccoli is the best for your microbiota whereas cabbage is the best for my microbiota,” he concludes. “But in general, if you eat a diverse diet that contains plant polysaccharides, eventually you are going to help the good guys

Hands on with Food and Farming

It’s a bright summer afternoon in 2016, and UW–Madison undergraduate Donale Richards accompanies a small group of high schoolers on a visit to the UW Dairy Cattle Center. They meet the cows — with a mix of excitement and trepidation — and peruse the milking equipment to fully appreciate what goes into milk production. The group then finds itself in a sunlit room occupied by a single Holstein. She has a small, circular door in her side — a fistula.

Donale Richards

Donale Richards took part in PEOPLE for a decade, starting in middle school and earning his UW-Madison degree in August 2017. (Photo by Sevie Kenyon BS’90 MS’06)

When their tour guide asks if they want to reach inside to feel the contents of the cow’s stomach, most students look unsure. Their noses wrinkle in response to the distinct aroma of the barn and the unusual opportunity in front of them. But one young man steps up to be the first. He reaches inside, a look of awe on his face as he clutches the remnants of the cow’s recent meals. Not to be outdone, Richards follows suit, announcing, “Well, I better give it a try!”

An incoming senior at UW–Madison at the time, Richards was serving as a coordinator for PEOPLE (Pre-college Enrichment Opportunity Program for Learning Excellence), which introduces underprivileged teens to the UW–Madison campus, a place they may otherwise know little about. His group of students was taking part in the food and agricultural sciences arm of the program.

Throughout their stay on campus, the students saw many aspects of what the university has to offer. But that summer day in 2016 they learned about a quintessential Wisconsin animal — the dairy cow. They also got the chance to experience some of what researchers do. The contents of cows’ stomachs are studied for a number of purposes, including identifying ideal diets, improving milk production, and understanding bacterial communities in the gut. This is why some cows are implanted with fistulas, which serve as a painless and sealable passageway to the gut. The awed (and disgusted) high school students had a rare chance to see — and feel — that research firsthand.

“This was certainly their first chance to reach inside a cow’s stomach, and for most, even just walking into a dairy barn is a new experience,” Richards says.

PEOPLE has been providing opportunities like these since 1999. A college pipeline for students from socioeconomically disadvantaged backgrounds, PEOPLE provides college preparation services and builds academic, interpersonal, and communication skills while also helping students explore academic and career interests. More than half of the program’s students are admitted to UW–Madison, where they receive a four-year tuition scholarship. The program’s first-year retention rate for college scholars is around 90 percent.

For high school students in the program, the summer provides a chance to live in campus dorms and become fully immersed in the college experience. As soon-to-be, or “rising,” sophomores and juniors, students stay on campus for three weeks. Rising seniors take part in a five-week curriculum that includes an internship or research experience. All of these programs are meant to give students who may otherwise not think about college a chance to explore and consider it for their futures.

“It’s very rigorous for these students,” Richards says. “They are living away from their families, and it can be difficult at first. But it’s a great exposure to the campus, and living in the dorms is their first opportunity to experience the university.”

Richards knows about the experience firsthand — he is a PEOPLE scholar himself. He took part in the program for a decade, starting in middle school and earning his UW–Madison degree in August 2017. As a coordinator of the summer program, he also served as a role model for its high school students — an up-close example of someone who had benefited from the PEOPLE program.

“The biggest thing I think I’ll take from the PEOPLE program is the network,” says Richards. “I saw different kinds of opportunities and met people I would have never met. It has really influenced me to make better decisions about what I want to do with my life. And now I get to share those lessons with new students as they go through the program.”

PEOPLE student eating ice cream

For PEOPLE students, a tour of Babcock Hall always ends with ice cream and a smile. (Photo by Beth Skogen)

 

Rising Juniors: The Three-Week Program

CALS has been involved with the PEOPLE program for several years, providing internship opportunities for high school students entering their senior years. In 2012, CALS partnered with PEOPLE to develop a program that introduces incoming high school juniors to careers in food and agriculture while providing a more complete exploration of the various fields they can pursue.

Their days are spent in a variety of settings. In the mornings, students attend classes to improve math, science, writing, study, and life skills, and they dedicate afternoons to exploring food and agriculture through field trips, lectures, and workshops. For many, these hands-on experiences are the most memorable and are best at helping them understand potential careers.

For one of the 2016 cohort’s first field trips on campus, they visited the F.H. King Student Farm, located near the Eagle Heights apartments on the west end of campus. Under clear blue skies, volunteers from F.H. King Students for Sustainable Agriculture showed their young charges around the half-acre plot and introduced them to a variety of plants. The PEOPLE students excitedly pulled carrots and beets from the ground, some expressing amazement at how familiar foods look while growing.

Other field trips included a visit to the aforementioned Dairy Cattle Center and a trip off campus to the Farley Center, a nonprofit organization located just outside of Verona, Wisconsin, that promotes ecological sustainability, social justice, and peace. Each of the field trip locations introduced PEOPLE participants to students, faculty, and professionals working in food and agriculture.

When asked about their favorite parts of the program, it’s clear the students find the hands-on experiences and field trips to be the most enjoyable — and the most effective. Many students named the Dairy Cattle Center and the garden and farm tours among their favorites, and almost all of them appreciated the interactive learning.

For Tom Browne, CALS senior assistant dean, this introduction to food systems is an important part of the food and agriculture program. He wants to connect students to fields they may otherwise think little about.

Students and organizers with the PEOPLE program visit the Farley Center in Verona, Wisconsin, as part of a session focused on food and agriculture. (Photo by Beth Skogen)

“A lot of these students come from urban areas, and they completely dissociate themselves from agriculture and what they think CALS is all about,” Browne says. “We try to provide programming that shows them how it affects them and their communities. We want them to have a greater understanding and appreciation of the agriculture world. We try to make those connections for them.”

And this is precisely the outcome for many students. As one wrote bluntly on a program evaluation, “When I first came into the class, I thought I’d hate it, but it was actually really fun, and it’s now something I’m interested in.”

Shaping students’ perspectives about agriculture was part of the master plan for Steve Ventura, a professor of soil science and environmental studies, and one of the main drivers behind the PEOPLE food and agriculture program. He was lead author of a U.S. Department of Agriculture grant that established the Community and Regional Food Systems project. This project, which brought together several universities, UW– Extension, and dozens of community partners in eight cities to foster innovation in urban food systems, includes PEOPLE as one of its educational arms.

Inspiration for the grant and the PEOPLE program involvement came from Will Allen, the founder and CEO of Growing Power, a national nonprofit organization based in Milwaukee, Wisconsin, that supports people from diverse backgrounds by helping to provide equal access to healthy, safe, and affordable food. Allen strives for what he calls the “Good Food Revolution,” a plan to grow healthy food and, in turn, healthy communities.

Ventura wanted to instill those same messages in students and use some of the grant money to develop the program in partnership with PEOPLE. “Food, or at least healthy food choices, are limited in some areas,” he says. “The idea of taking control of the food system and having independent choices is important. If nothing else, we want to make people, especially young people, more aware of the opportunities to have more say in their food systems.”

PEOPLE students examine the equipment in the milking parlor at the Dairy Cattle Center on the UW–Madison campus. (Photo by Beth Skogen)

Rising Seniors: The Internship

Once they reach their third year in the food and agriculture program, seniors take part in an internship that provides an even larger window into food systems. In recent years, interns created a healthy, frozen pizza, taking the project all the way from raw ingredients through the preservation and packaging stages. Greg Lawless, an outreach program manager with UW–Extension who oversees the internship, has worked for the past two years with Will Green, founder and executive director of a Dane County youth mentoring program called Mentoring Positives, to create the product.

“I was seeing a gap between growing food and eating the food, so I helped develop an internship around food science,” Lawless says. “Food processing, making nutritious food and getting it out to communities, is a big need, and a great opportunity for companies and researchers. In 2015, we came up with a whey protein bar, and the past two years were devoted to the frozen pizza project.”

Seniors and students from the Mentoring Positives program work closely with Lawless as well as volunteer undergraduates and faculty and staff members from UW–Madison and Madison College to plan and devise their food product. They also visit with chefs and other food development experts.

“We really have a giant team supporting us,” Richards says. “The kids get to meet with important players in the industry, and the industry, in turn, gets to inspire the next generation of professionals.”

In 2016, the interns took what they learned back to the UW Food Application Lab in Babcock Hall to develop each component of their pizza, from the dough and sauce to the cheese and toppings. After a couple of weeks of learning and experimenting with their pizzas, the seniors invited Richards and the juniors to taste their creations. The joint session gave the juniors a chance to see what they could be working on the next year as interns, and it gave the pizzamakers valuable feedback that they used to tweak their product.

At the end of their summer session, rising seniors took part in a pizza launch party at the Salvation Army of Dane County, where Green and his Mentoring Positives students welcomed the PEOPLE program and honored guests, including potential partners and donors. The students presented their pizzas, including production and marketing strategies. As guests taste-tested the pies — ranging from spinach and tomato to green olive and mushroom — the students sat down to talk about their experiences in the program. Their enthusiasm shone as they reflected on the summer and indulged in their creations.

Student sampling peas

A PEOPLE student samples the peas grown at the Farley Center in Verona, Wisconsin. (Photo by Beth Skogen)

Some of the interns began to sound like connoisseurs. “This was all influenced by traditional Italian pizza,” one student says. “A major focal point was to create it from scratch to ensure a healthy frozen pizza. We have only vegetable toppings, wheat in the crust, no sugar in the sauce, and less cheese than most frozen pizzas.”

Another student gushed about the power of collaboration. “The pizza is gorgeous. It didn’t start out this way, but now it’s absolutely beautiful to see our product. The cool thing is we had PEOPLE program kids, Mentoring Positive kids, UW kids, so we tried to blend different people’s tastes together. I’m trying to not be too sentimental because this is so different than when we first started. This tastes like it was professionally produced, and it’s crazy to say that we did this!”

Another boiled his satisfaction down more succinctly: “Dude, this tastes amazing.”

The PEOPLE Program’s Lasting Influence

The positive feedback and enthusiasm of the students is what excites Browne. “I see a lot of really talented and motivated students come through the program,” he says. “It’s energizing to be reminded that there are a lot of talented kids out there who just need some encouragement. Watching them have these light bulb moments is really rewarding.”

Lawless has also found his work with PEOPLE students gratifying. Not only is he able to teach and mentor rising seniors through their internships, he also works with PEOPLE scholars after they become UW students.

Students harvesting beets

Interacting with familiar foods like beets and carrots while they are still growing is a new experience for many PEOPLE students, one they get to indulge in at the F.H. King Student Farm on the UW–Madison campus. (Photo by Nik Hawkins)

“I have been on campus for 26 years, and I’ve worked with tons of students,” Lawless says. “Five of the best have been PEOPLE scholars, and Donale is the latest in a long line of really exceptional undergraduates. Even once they get into their careers, we want them to come back and interact with new PEOPLE students.”

That network of support and encouragement exemplifies the benefits of PEOPLE and the goals of the food and agriculture program. CALS faculty involved in the program hope that more students are able to take advantage of the opportunities provided by the program and find their passion. For Isaiah Gordon, a junior in 2016, this is exactly what PEOPLE provided.

“The rigorous classes have prepared me for the upcoming year so that I can go above and beyond in school,” Gordon says. “One class I found particularly great is the food systems course. It provided me with hands-on experiences that promote health and sustainable food. It has changed the way I eat and how I view the world. There were many field trips that gave me the opportunity to explore different careers in the food system. I recommend anyone get familiar with the food system because this ultimately can help our society in the future.

Steve Ventura, a professor of soil science and environmental studies who was one of the main drivers behind the PEOPLE food and agriculture program, participates in a “pizza launch party” with the students who developed the recipes. (Photo by Sevie Kenyon BS’90 MS’06)

“The PEOPLE program also gave me the opportunity to connect with others and meet new friends. I can’t think of any other program that gives me all the benefits this program gives. I’m glad to be part of it.”

Experiences like Gordon’s speak to the heart of what PEOPLE and CALS are trying to achieve. And it’s a mission that Richards takes pride in forwarding. Richards graduated in August 2017 with a degree in biological systems engineering and also spent time during the 2017 summer with the PEOPLE program — this time working with Mentoring Positives students as the pizza project manager. He says he hopes to remain involved with the PEOPLE program as much as possible.

“I love working with PEOPLE students and giving back to the program that brought me into this university,” Richards says. “I’m actually able to teach them and advise them on healthy lifestyles, and to me, that’s so important for minority communities because they don’t often have that type of role model. “So the more people we get into this field, the more people we’ll impact in the long run. It’s important to me to get youth involved in projects like these because they get the exposure they might not get otherwise, and we can give them the ability to return to and improve their communities.”

Beyond Antibiotics

Since the beginning of their widespread adoption in the 1940s, antibiotics — the antimicrobial drugs we use to treat bacterial infections — have saved millions of lives. In recent years, however, misuse and overuse of these drugs in human medicine have helped put us on the path to a worldwide crisis. In this environment, harmful bacteria can evolve more rapidly, developing higher and higher levels of resistance. As a result, our “wonder drugs” are losing their effectiveness. This leads to longer and more complicated illnesses; greater risks for spreading infections; more hospital visits; the use of stronger, costlier, and more toxic drugs; and, ultimately, more deaths. Fortunately, scientists at CALS are facing this challenge head-on. From alternative forms of treatment to better methods of infection detection, here are some of the solutions they are working to bring to the world of modern medicine.

Friendly Microbes

Microbiologist Jan Peter van Pijkeren looks at probiotics — those microbes thought to provide health benefits in our bodies — as more than just friendly bugs. He sees them as a way to sneak in antibiotic-free treatment for disease-causing bacteria like Clostridium difficile.

Jan Peter van Pijkeren works with Laura Alexander, a doctoral student of microbiology, in his lab. (Photo by Tim Fitch)

Known as C. diff, this resilient gastrointestinal pathogen causes stomach pain, diarrhea, and potentially life-threatening inflammation of the colon. But by loading the probiotic bacterium Lactobacillus reuteri with viruses targeted at C. diff, van Pijkeren aims to deliver genetic instructions that cause the pathogen to self-destruct.

In an ironic twist of fate, C. diff often colonizes the gut after antibiotics wipe out the microbial communities that normally keep it at bay. Infections often happen in hospitals, where antibiotics are becoming more common. Additional antibiotic treatments targeting C. diff don’t always work, and the infection recurs in as many as 20 percent of patients.

“The downside of antibiotics is they are a sledgehammer that depletes and destroys the gut microbial community,” says van Pijkeren, an assistant professor of food science. “You want to instead use a scalpel to specifically eradicate the microbe of interest.”

Van Pijkeren thinks that L. reuteri, a probiotic bacterium found in many foods and the intestines of most animals, could be that scalpel. His team was able to amplify by 100-fold the natural ability of their strain of the bacterium to survive its trip through the harsh environment of the gut, making it a good candidate to deliver antibiotic-free treatments to the intestines where C. diff resides.

Van Pijkeren’s idea, in collaboration with Rodolphe Barrangou of North Carolina State University, is to use one of C. diff’s own defense mechanisms, called CRISPR, against it. CRISPR is a genetic surveillance system that bacteria use to protect themselves from invading viruses, which inject DNA into bacterial cells to attempt to replicate. If a bacterium has the right sequence of DNA to match an invading virus, it can use the CRISPR system to cut the viral DNA, thereby inactivating it and preventing infection.

Scientists have used this ability to cut specific sequences of DNA to genetically engineer a wide range of organisms for research aimed at developing new therapeutics. The van Pijkeren lab, which has been developing CRISPR to genetically engineer L. reuteri, now wants to co-opt the system by delivering DNA that targets C. diff’s own chromosome. That DNA will be injected by C. diffspecific viruses, which will hitch a ride with L. reuteri into the intestines.

If it works, C. diff will unwittingly cut and degrade its own DNA, preventing the pathogen from multiplying and doing more damage. Because both the viruses and the genetic instructions are targeted at C. diff, Pijkeren believes no helpful bacteria should be harmed.

Working with Barrangou and funding from the National Institutes of Health, van Pijkeren has engineered L. reuteri to produce viruses that target lactic acid bacteria, an initial step toward getting the probiotic to produce C. diff-specific viruses. They are also developing ways to induce the probiotic to release these viruses at the right time inside the gut. If these lab tests go well, van Pijkeren’s goal is to start testing the system in a mouse model of C. diff infection soon.

“I think it’s pretty fascinating that an organism like Lactobacillus in such low numbers and small amounts can actually have a health benefit,” van Pijkeren says. “To then exploit these microbes to deliver therapeutics is very appealing because we know humans have been safely consuming them for thousands of years.”

“Grazing” Amoeba

Bacteria have developed an uncountable number of chemistries, lifestyles, attacks, and defenses through 2.5 billion years of evolution. One of the most impressive defenses is biofilm — a community of bacteria enmeshed in a matrix that protects against single-celled predators and antibiotics. But there’s a way through every suit of armor, and professor of bacteriology Marcin Filutowicz has found one.

Along with Dean Sanders, presently at the Wisconsin Institute for Discovery, and patent co-inventor Katarzyna Borys, Filutowicz has shown the first proof that a certain group of amoeba called dictyostelids (“dicty”) can penetrate biofilms and eat the bacteria within. In a recent study, the researchers pitted four types of dicty against biofilm-forming bacteria that harm humans or plants. For example, they targeted Pseudomonas aeruginosa, a common, multidrug-resistant bacteria that afflicts people with burn wounds or cystic fibrosis, and Erwinia amylovora, the cause of a devastating disease known as fire blight in apple and pear trees.

 

As expected, the results depended on the strain of dicty and the bacterial species. In several cases, the dicty completely obliterated thriving biofilms containing millions of bacteria, all of it captured in time-lapse, microscopic movies, the first of their kind. In addition to the cinematic evidence (see video above), other indicators of successful attacks against all four species of bacteria include spore germination and the subsequent union of single-celled dicty into a multicellular “slug” (a striking trait that has earned dicty the label “social amoeba”).

Filutowicz became interested in dictyostelids after discovering a neglected archive of about 1,800 strains amassed by Kenneth Raper, a UW–Madison bacteriology professor who discovered the soil-dwelling microbes and started collecting them in the 1930s. He found that Raper and his team were feeding and growing dictys in the lab using bacterial prey, but nobody had pursued their commercial potential as microbe hunters.

“They grow on E. coli [a common resident of the human intestine], and I quickly realized that, because dicty are not pathogenic, we might use them as a biological weapon against bacteria.”

Marcin Filutowicz (Photo by Allan Attie)

Since 2010, Filutowicz has learned a good deal about how dicty “graze” upon bacteria, and which ones they prefer. “We looked at how these cells dismantle biofilms, trying to understand what physical, chemical, and mechanical forces deconstruct the biofilms, and how the dicty move in 3-D space,” he says. “These are phagocytes, and they behave much like our own immune cells, except our immune cells do not break down biofilms.”

His collaborator, Curtis Brandt, a professor of ophthalmology and visual science at UW–Madison, has produced promising results suggesting that the organisms are harmless to rodents. Now, the National Institutes of Health have given them and AmebaGone a $1.5 million grant to support their research on using dictys to fight bacterial keratitis, an eye infection, first in rodents and then in rabbits and humans.

“This medical application has a lot of promise,” Filutowicz says.

More near-term use for dicty are found in agriculture. In 2010, Filutowicz formed AmebaGone. With funding from the National Science Foundation, the firm has been advancing dicty products toward commercializations, including treatments for fire blight and other bacterial infections of crops.

“Our 2017 external field trials for fire blight treatments were very promising,” says Chad Hall, a senior scientist and director of AmebaGone’s fire blight project. “Several of our dicty-based products reduced fire blight disease without harming either trees or fruit. In fact, one of our treatments was as effective as the antibiotic streptomycin, which is the gold standard treatment for fire blight control in conventional apple orchards but is now banned in organic apple production.”

Infection Detection

One way to prevent the overuse of antibiotics, and the drug resistance it creates, is to determine when treatment is not needed. And that’s one of the benefits of a new system developed by Isomark, a UW–Madison spin-off company, and its founder, Mark Cook.

Isomark’s system measures carbon isotopes in exhaled breath. Without even touching the patient, it can offer the earliest warning of severe bacterial infection, says Cook, a professor of animal sciences. He founded the company in 2005 along with Warren Porter, a professor of zoology; nutritionist Dan Butz; and others.

Their novel detection device can often spot a bacterial infection before the patient feels symptoms, increasing the potential for faster, better treatment for severe infections. The company is focused on intensive care units (ICUs), which treat about 5 million people in the United States each year.

Antibiotic-resistant bacteria like MRSA (methicillin-resistant staph aureus) are an accelerating problem in hospitals, says Isomark CEO Joe Kremer. “The average hospital stay is five days, but it’s 20 days with a hospital-acquired, resistant infection. The healthcare industry puts the cost of diagnosis, treatment, and the extended stay at $35 billion to $88 billion.”

Isomark’s analytical instrument offers earlier detection of bacterial infection by measuring the ratio of carbon isotopes in patients’ breath samples. (Photo by Ben Vincent)

These figures do not account for the pain, worry, and deaths associated with these severe infections. About 100,000 Americans die of a hospital-acquired infection each year, Kremer says, and ever-more stringent controls have not brought the problem to heel. But earlier detection may help.

When the immune system responds to an infection, subtle changes in the ratio of the common carbon 12 isotope and the rare carbon 13 can be detected long before a doctor, a blood test, or even the patient knows that an infection is present. (Isotopes are chemically identical versions of an element that can be distinguished by their differing masses.)

After gathering breath samples and medical records from 100 ICU patients, Isomark scientists saw a telltale change in the isotope ratio for each patient who became ill. “Our studies show that we are 18 to 48 hours ahead of when clinicians suspect an infection,” Cook says.

Rapid detection offers multiple benefits, he adds. This includes earlier treatment, which can reduce the ill effects that come with a severe infection, and earlier guidance for physicians about the need for tests to determine the location and cause of an infection. It can also lead to less antibiotic use.

Because bacterial infections are a major hazard in ICUs and operating rooms, “Antibiotics may be thrown at every patient after surgery as a preventive, but that is actually breeding resistance,” Cook says. “If a breath test comes back negative, antibiotics may be unnecessary.”

Since the test measures nonradioactive isotopes in exhaled breath, the procedure is noninvasive and safe. And the testing process could hardly be simpler. The patient breathes into a bag, or a sample is grabbed from a ventilator. The bag is connected to the tester, the patient ID is punched in, and results appear in 10 minutes.

Isomark is seeking FDA approval as a medical device and is gearing up for a final “regulatory trial” that will look at 300 patients in up to six hospitals nationwide. “We can’t be sure about the FDA’s decision, but the agency has been very positive,” Kremer says. A decision could arrive in January 2018.

EDITOR’S NOTE

We are sad to report that Professor Mark Cook passed away in early September due to complications of cancer. He will be deeply missed by the CALS community and beyond. Read more about his life and distinguished career as a teacher, mentor, entrepreneur, and groundbreaking researcher in the realms of food production and animal health.

Wading through Mendota’s Mysteries

It was a silly question, so Trina McMahon laughed. What’s more important: a lab coat or a Twitter handle? “Twitter handle, for sure. We don’t do anything anymore in the lab,” she says. “Probably a pair of muck boots is even more important. You’ve got to get dirty in the field and get your samples, and then maybe spend a day in the lab, but then you spend the rest of your time in front of a computer.”

Microbial ecologists like McMahon use computers as their eyes. The bacterial communities they study — microbiomes in the human gut, in a Yellowstone geyser, in Lake Mendota — are almost entirely invisible. How, then, to see? “What we’re spending so much of our time doing in microbiome research is natural history, what the plant ecologists were doing 120 years ago, running around with their field notebooks,” says the Vilas Distinguished Achievement Professor with appointments in both bacteriology and civil and environmental engineering. “Only our field notebooks are our sequencers.”

It’s the first golden age of microbiome discovery, and this generation of microbiologists has little need for a microscope. Instead they use increasingly sophisticated techniques to read the genetic code of entire ecosystems, running complex statistics on powerful computers to sketch their specimens. It’s undoubtedly a paradigm shift — in humans, for example, it’s been suggested that the human microbiome is so important to human health that it’s like discovering a new organ system.

Could the next breakthrough come from Lake Mendota?

Sam Schmitz BS’17 collects water samples near the buoy marking the Mendota Deep Hole, the deepest part of the lake (about 25 meters). (Photo by Sevie Kenyon BS’80 MS’06)

 

 

***

Lake Mendota is often called the most studied lake in the world. That’s in part because Edward Birge and Chancey Juday helped launch the science of limnology at the University of Wisconsin. The Center for Limnology has been a locus of world-class ecological research for decades, developing some of the most complex ecological models in the world.

It now also happens to be the lake with the world’s most amassed microbial data thanks to 18 years of methodical sampling now overseen by McMahon’s lab. This shared focus on Lake Mendota implies a certain kinship of purpose, but it also stokes a friendly intellectual rivalry.

McMahon knows all about Lake Mendota’s fabled scholarship, but she has her critique: those models ignore microbes. The limnologists say that the microbes are always there, in pretty much the same numbers, and they always do pretty much the same thing: turn dead things back into their constituent nutrients and carbon dioxide. Why worry about them?

“I think Trina has been very bold in being willing to do the Birge and Juday thing, the pure descriptive phase of it,” says recently retired UW Center for Limnology director Stephen Carpenter. “As a basic science enterprise, I totally support it.”

At the same time, he acknowledges it wouldn’t be hard to find ecologists who would question the return on investment so far. “That kind of modeling is very important,” McMahon acknowledges in return. “But it glosses over all of the mechanism. I want to understand the mechanism.”

Just one example: over the last decade, microbial breakthroughs have rewritten our understanding of the nitrogen cycle, the natural processes that convert nitrogen in the environment into different chemical forms. “Because there may be something in the mechanism that fundamentally changes the coarser scale models in a way that you can’t predict.”

“Respect the microbes” is a motto printed on the back of one of Trina McMahon’s T-shirts. (Photo by Sharon Vanorny)

 

***

Robin Rohwer winces as she opens her laptop to launch R Studio, an interface used for statistical programming. Her left middle finger is broken and bruised, the result of an epic race-day capsize in Lake Mendota. It was so windy the race was canceled, and five of the six sailboats dumped on their way back in.

A lifelong lake junkie, Rohwer knows lakes, the look and feel of them. If you told her what microbes were present, she could probably tell you the color of the water. But if you broke out mugshots of Lake Mendota’s most common bacterial species, she wouldn’t recognize a single one. For a fish biologist or a botanist, that would be unthinkable.

Rohwer uses R Studio as her X-ray spectacles. She wasn’t a programmer when she started in McMahon’s lab in 2011, but now she has a library of personal code. “I just make a loop and look at it in a ton of different ways,” she says. By season, by week, by top 10, by temperature, depth, and light intensity.

The resulting kaleidoscope of graphs are exploratory plots that guide her toward a more intuitive understanding of the data. “When I visualize them, what I see in my head is the curve over time,” she says. “Is it spiky? Is it smooth? That’s how I think. Even if you don’t see a pattern, it gives you an idea of something to start with.”

It’s a necessary perspective given the crazy diversity of microbes. Rohwer’s been trying to decode 11 years’ worth of bacterial samples collected from the deepest point in Lake Mendota between 2000 and 2011. The mission: identify everything in these 95 samples.

During this time, as many as 29 fish species were found in the lake alongside 18 species of zooplankton and 16 species of aquatic plants. For microbes, the magic number might be 17,437. That’s not 17,437 species, but 17,437 OTUs, or operational taxonomic units. “We can’t use the word species because that’s taken by the microbiologists,” she says. They have very strict definitions of a microbial species. “But we need to call it something in order to work with it.”

Microbes facilitate the cycling of almost every nutrient through the lake ecosystem, and their DNA contains signatures of these chemical reactions. Rohwer uses these signatures and other genetic fingerprints to sort the microbes into OTUs. What emerges is a rough picture of “who” is probably doing what.

While the majority of bacteria survive using fairly basic life chemistry, bacteria are so prolific and diverse that you can’t rule out the possibility of something really funky, something you couldn’t even imagine. It’s microbes, after all, that have evolved to survive temperatures above boiling and to tolerate toxic heavy metals. “Microbes are crazy diverse,” McMahon says. “We don’t know if 17,437 actually means that there are truly 17,437 different ways of making a living in the lake, or 25. That’s one of the things that we’re trying to figure out.” Those 25 OTUs are the most common threads, present most of the time, and clearly the workhorses of the lake.

Then there’s the remainder, making up the majority, called the “long tail” because that’s what their frequency of occurrence looks like when plotted on a graph. Most of these 17,437 OTUs occurred only once, on one day, but this rare biosphere makes up a huge proportion of the data set. “What is this deep diversity doing in the ecosystem?” Rohwer asks. This is a primal question driving microbial ecologists, but she just shrugs: not enough data.

Realistically, they have little idea of what even the common bacteria do. Consider AC1, by a long shot the most prosperous family of bacteria in Lake Mendota. “AC1 is just so abundant and nobody knows what it does,” Rohwer says. But here’s the kicker: Twenty-five years ago, nobody even knew that AC1 even existed.

 

***

In the beginning, there was the Great Plate Count Anomaly. Early microbiologists noticed that while microbes were abundant and ubiquitous, most of them would not grow in the lab. Even today, it’s estimated that fewer than 1 percent of bacteria sampled from the environment can be cultivated using standard laboratory methods. It wasn’t until sequencing breakthroughs in the 1990s that scientists could begin to close in on these cryptic microbes.

The most amazing story of microbes hiding in plain sight is an order of tiny oceanic bacteria called SAR11. Until 1990, SAR11 was nothing more than microbial dark matter. But once its genetic signature was catalogued, SAR11 was discovered to be prolific beyond belief — numerically, its various species comprise about half of the microbes in the ocean. When they discovered a virus that infects SAR11, it took little more than a back-of-the-envelope calculation to declare it the most abundant organism on the planet. This is how a microbe shakes up the world.

Before long, the hunt was on for a freshwater equivalent to SAR11. DNA from AC1 was first recovered from an Arctic lake in 1996, and since then it has been discovered in every lake that’s been examined. Like SAR11, it is dominant, particularly in Lake Mendota, which McMahon calls an AC1 factory. “They’re so small that sometimes people probably thought they were viruses,” she says. “We knew that there was something, but we didn’t know their names or anything about them.”

When Alexandra Linz arrived in McMahon’s lab in pursuit of her Ph.D., McMahon suggested a high-risk, high-reward project: cultivating AC1. It’s never been done, and success could launch a career. Every month or so Linz collected another sample from Mendota and she’d inoculate another 96 cultures, each recipe unique. She’d return a month later, but nothing took. After a year of this — more than a thousand tries — Linz realized that the potential number of variables in play compounded to a frighteningly large number. She wanted a Ph.D. project, not a lottery ticket, and moved on to broader survey work comparing lakes in northern and southern Wisconsin.

Basic comparisons can be made by using different sets of sequencing data, such as DNA and RNA. “Looking at the genomes is like looking in someone’s toolbox,” Linz says. “You can probably tell what profession they are, a woodworker or a plumber, just by what tools they have in their toolbox. But looking at the RNA is like looking at what tools they have out on their workbench. What are they doing right now?”

Her Ph.D. work is focusing on the role of microbes in carbon cycling in lakes (an area of particular value in understanding climate change). But along the way she also got involved in looking at seasonality — how the microbial community changes from year to year. Seasonality is one of the baseline rhythms of biology, patterns that humans have probably observed since even before we became humans. Seasonal variation, particularly in lakes that ice over regularly, is a cornerstone of lake science.

Surprisingly, Linz found no seasonality in the microbes that live in a certain kind of lake in northern Wisconsin. “I’ve looked at the data every way I can think of to try and find a seasonal trend, but I haven’t been able to find one,” she says. Previous studies had found seasonality in other kinds of lakes, but they’d also noted a higher degree of variability in summer. “Maybe it’s not so surprising that we can’t predict the summer community based on the previous year,” Linz says. But still, the finding hints at a layer of difference and complexity separating microbial ecology and its coarser-scale cousins.

Is there a longer cycle or a more complex link to weather that can’t be seen because we haven’t been looking long enough? Or maybe, after another decade of research, we’ll realize that it’s just a dice roll? “We know there is an element of randomness in microbial communities,” Linz says, apparently only a little frustrated by the endless enigma. “I think it’s really fun that there is so much unknown about microbial ecology. It’s a young field, and there’s a lot we still have to discover.”

 

***

Linz’s efforts to cultivate AC1 in the lab were not wasted. A few cultures produced a drastically reduced mix of microbes, including AC1, and were sequenced to figure out if cooperation was their survival secret. Then Sarahi Garcia, a visiting scientist from Uppsala University in Sweden, helped McMahon’s lab sequence a single AC1 from Lake Mendota, part of a search for the light-sensing protein rhodopsin, which had been found in other AC1 specimens. Already well understood because of its sensory role in vision, there’s also growing evidence that, in microbes, rhodopsin doesn’t just sense light but can also capture its energy.

This is not in your father’s biology textbook, and it probably wasn’t in yours, either. Microbes are infamous for all kinds of funky metabolic tricks, but this could change the way we think about lakes. “It’s a way to get energy without using chlorophyll,” McMahon says. “There could be all of this biomass and energy generation going on that we’re not accounting for in our models that assume chlorophyll is a main driver.”

The best way to prove it would be to create a pure culture of AC1 and show that it can survive on light alone. But recall the Great Plate Count Anomaly and how nobody has successfully cultured AC1. That leads you back to the genome.

AC1 has a very small genome, McMahon says: “Like crazy small, endosymbiont small.” She’s talking about bacteria that evolve in a symbiotic relationship with an organism and rely on their host for so much that they can afford to jettison many genes. “To find a genome that small in a free living organism is weird.”

So AC1 is incredibly abundant, which is to say, highly successful. It also has a very small genome, but its genes include the ability to manufacture rhodopsin. So it stands to reason that the rhodopsin is doing something. But what?

To help unravel the puzzle, McMahon approached her UW colleague Katrina Forest, a bacteriologist who studies photoreceptors — proteins that respond to light. Forest was intrigued by the science and tickled by the implication that everything we understand about the equations for carbon and energy balance in lakes, and not just Lake Mendota, may be askew. “I love it when you realize that, even in our advanced times, when you can justifiably think we’ve already solved most of the big problems, that there
is something so completely not appreciated and novel,” Forest says.

Forest’s lab has been hard at work teasing out details on a molecular level, getting closer to understanding what the rhodopsin is doing. “We still don’t have any proof that AC1 is doing primary production in the lake, but it certainly has got all of the jigsaw puzzle pieces,” she says. “This organism is encoding this phototrophy system that really is brand-new in terms of understanding how the lake ecosystem keeps itself alive.”

A similar investigation is playing out in the oceans over SAR11, which also has a rhodopsin structure. Dueling calculations disagree over whether primary production is even possible, though McMahon says that the current consensus is that SAR11 isn’t doing much of it. One theory is that the rhodopsin may help the microbe survive extreme conditions.

“Nobody has done the calculations in lakes, and I’m not even convinced that the calculations they have done in the ocean really account for everything,” McMahon says. She’s not willing to declare victory on her AC1 primary production theory, but neither will she concede.

“If they didn’t have this, then they probably wouldn’t be so ubiquitous and abundant,” she suggests. “I think it’s still open. I mean, that’s your sense of mystery, right?”

The preponderance of evidence in Lake Mendota is clear: phosphorus is the problem. Too much phosphorus leads to an overgrowth of algae, which leads to stinky, pea green lakes. Even McMahon concedes, yes, phosphorus is the driver, the catalyst, the baddest of actors.

Robin Rohwer uses a power auger on Lake Mendota to drill a hole through the ice for water sampling during the winter of 2015.
(Photo Courtesy Robin Rohwer)

 

 

And yet, she really thinks we should be paying more attention to nitrogen. Partly this is about her fascination with AC1. They clearly play a role in the nitrogen metabolism of the lake. But she’s also shown that nitrogen may well play a role in the eruption of cyanobacteria that have the ability to turn the lake from merely unpleasant to toxic.

To understand how, you need to envision summer, when the lake is stratified — warm water on top, cool down below. This happens because as water warms it expands and gets less dense. The density difference is so extreme that, once a lake stratifies, the warm and cold regions can’t be mixed until the top layer cools in the autumn. Stratification has profound effects on almost everything in the lake. The top layer keeps refreshing its oxygen by mixing with the air. Dead things drift slowly to the bottom to rot. Before long, the oxygen in the bottom layer gets used up. The microbial community switches into anaerobic decomposition.

“So down at the bottom you’ve got all these microbes cooking, breaking down the dead stuff, making those nutrients available again, but they’re trapped down there until the fall,” McMahon says. In that autumnal mix, the entire lake rapidly becomes saturated with oxygen and nutrients. Quite often there are huge, nasty cyanobacteria blooms, but these go largely unnoticed because people aren’t boating or swimming.

Then the lake, well mixed with oxygen and nutrients, freezes. There’s not much sampling under the ice, but the microbes are still active until, eventually, the spring thaw comes. Nitrogen can take many forms in the environment; in the fall, ammonia is abundant but gets gradually converted under the ice to nitrate. How early the ice forms and how long it stays influences the ratio of ammonia to nitrate at ice off.

Phytoplankton, or regular algae (not the cyanobacteria), prefer ammonia, so they’ll consume that first, then start to work on the nitrate. This ratio between ammonia and nitrate, combined with climatic conditions, seems to be a trigger for cyanobacteria bloom. Underneath the ice, the nutrients from the previous summer sit, an echo in the system. McMahon sees this nitrogen reverberate through the microbes in the lake, a rolling mix of cause and effect, and revels in the effort to untangle it all from a background of climate change, land use, and natural variability. “It’s possible there is a pattern that we haven’t seen because we haven’t been looking long enough,” she says. And then she laughs: “That’s the usual basic science cop-out.”

She dreams about finding the key to making all cyanobacteria go away, some microbial trick to starve it of phosphorus, but she knows her field is just at the very beginning of even being able to imagine such innovation. “I want to be able to do something to the system to fix it, not just study it,” she says. “But we’re pretty far from being able to do something like that.”

 

***

Lake Mendota through the eyes of Trina McMahon is a bit of a paradox. The lake has its seasons, but the microbes may not. It’s got incredible diversity, yet we can’t even name what’s there. Its most common species could be doing the most uncommon things with sunlight. And it’s got a phosphorus problem — but don’t forget the nitrogen.

“It has this reputation of being the most studied lake in the world, but it’s also kind of a weird lake,” McMahon says. With high calcium and magnesium concentrations, it’s not, chemically, an average temperate lake. It also has a diverse mix of agricultural and urban influences. “Taking what we know about Lake Mendota and extrapolating it to all the lakes in the world is very difficult because it is not really a textbook lake,” she says. “But it is the one in the textbook.” And she laughs again.

Indeed, Lake Mendota is at a difficult place in its history. In the last decade, it’s been hit with a succession of shocks, including two major invasive species and increasing precipitation from climate change. Water clarity is in decline again. State and federal support for research funding and environmental regulation is in serious doubt. Carpenter — perhaps the preeminent aquatic ecologist of his generation — is stepping down.

Carpenter’s not going to give microbes or microbial ecology a free pass. Ecologists know that basically all roads lead through microbes, that they are the gatekeepers in nutrient flow through ecosystems. Yet despite an enormous amount of effort, we still don’t know how those flows are blocked or limited or enhanced by different microbial groups. “It turned out to be a lot harder than anybody knew,” he says. “If you really want to know the rate of sulfate reduction, you might just be better off to measure the rate of sulfate reduction instead of worrying about who did it.”

But he also reminds critics that breakthrough understanding was lacking in all branches of ecology for a long, long time. “If we don’t really delve into this microbial structure question, we’re never going to bridge structure and function in the microbial world,” Carpenter says.

That’s the challenge for McMahon and her colleagues. On her docket right now is a closer look at how microbes affect mercury in the lake, and she also works downstream with wastewater treatment, where microbes help remove excess phosphorus from the system. Meanwhile, rapidly advancing technology combined with the ongoing in-depth lake studies have generated a backlog of data and hypotheses to test.

“There is just so much that we don’t know,” McMahon says. “Yes, it’s awesome because it’s the most studied lake in the world, and we’re famous for that reason. But we also don’t understand it at all. It’s weird. How can that be? We should g understand everything if it’s the most studied thing, right?

 

Sidebar: Data in the Depths

Investigating Lake Mendota’s microbial mysteries requires mining the water for data, but it’s not as simple as walking to the shoreline and dunking a bucket under the waves. It’s a long, meticulous process of equipment preparation, sampling, and storage.

Students working in Trina McMahon’s lab collect samples twice a week from “ice off” (roughly late March) to lake freeze (usually December). Each boat trip takes them to the buoy marking the Mendota Deep Hole, the deepest part of the lake, where they measure water clarity, sunlight penetration, pH levels, temperature, conductivity, dissolved oxygen, and barometric pressure. Next, they collect two water samples using a 12-meter tube, which yields an integrated sample of the entire water column down to that depth. Each sample is stored in a 4-liter container for transport.

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Back in the lab, a small portion of each sample is placed in a tube with a compound that prevents organic cells from bursting when frozen. These samples are preserved so individual cells can be extracted and put through genomic analysis in the future. Larger portions of each sample undergo a filtering process.

The filtered portions are frozen and used later to determine the nutrients present in the water at the time of sampling. The filters themselves (and everything they caught) are carefully folded, placed in small tubes, and frozen for future DNA extraction and genomic analyses. The readings taken during sampling and the steps taken throughout sample processing are all painstakingly recorded in a lab notebook and also entered into a database.

Candid Camera

At first there is nothing—windblown leaves maybe, or the quicksilver skitter of a squirrel. I can’t identify the source of the movement, and settle back expectantly because soon, I know, there will be more chances.

Huddled in the twilit hour I am hunting, expecting the common whitetail deer—but hopeful for more elusive game. Where there are deer there could be a wolf, right? A bear? Either would make the wait worthwhile. Or perhaps something I’ve never seen, like the elusive fisher?

Some time passes before I see the princely buck, so hale and burnished brown that my gaze lingers long in pure appreciation. His neck and shoulders are heftier than even the regal eight-point crown suggests. I’ve seen a lot of deer already, but he has presented broadside, at perfect range. My finger hesitates as I savor the action. And finally I decide, yes, this is a keeper.

I shift in my perch and refocus. Yes, there is the heart. My finger flexes. And I click on the heart icon. Subject 4988060, a Dane County buck snapped last November, is now in my favorites folder.

My hunting perch, you may now realize, is my customary recliner, and I’m using my laptop to spy on the wildlife of Wisconsin while dinner warms. In 20 minutes I’ll go through a few hundred of the millions of photos already collected by Snapshot Wisconsin, a growing net- work of trail cameras.

By now everybody’s seen trail cam photos. Maybe you or someone you know already uses them to scout deer, or just to see what’s on your land when you’re not looking.

Certainly someone’s emailed you a photo or short video, or they’ve shown up in your social media feeds. Those are the special shots, curated, viral. Snapshot Wisconsin is the raw feed, and therein lies the fun. Because here you can get your wildlife fix and be a scientist, too. Identifying these animals contributes to a cutting-edge effort that may fundamentally change the way we study wildlife.

“It’s like having 350 people out there in the woods day and night recording everything they see,” says Jennifer Stenglein MS’13 PhD’14, a research scientist with the Wisconsin Department of Natural Resources (DNR) who directs Snapshot Wisconsin. “That’s amazing data that we’ve never really had before.”

And 350 is just for starters. The goal is four cameras in every township in Wisconsin. Stenglein will be happy if they can reach at least 3,000 cameras. “We are, I believe, going to have one of the best data sets in the world,” she says.

At 10:40 every morning a NASA satellite flies over Wisconsin and snaps a series of pictures. The photographs measure many things, including a day-by-day record of how green the landscape is, which in turn gives us an idea of how well the plants are doing. The data has been collected for years—one of the satellites, Terra, has been in orbit since 1999—and offers an ever-lengthening perspective on the American landscape.

Satellite photos are now commonplace, but for most people remote sensing data is an abstraction. Woody Turner, program manager for NASA’s Ecological Forecasting, is always working to make that data matter to as many Americans as possible. “It’s really important to be able not only to understand what’s happening in your backyard or your woodlot but also to put it in the broader context,” he says. “The satellite brings in the broader context.”

In 2012 NASA announced it wanted to fund a project connecting its data with state agencies and university researchers. These are regular customers, but now there was a twist: NASA wanted a project that also used trail cameras and citizen scientists.

Phil Townsend, a professor of forest and wildlife ecology at CALS, had wanted to connect trail cams and remote sensing data for years, and he quickly called his professor colleague Ben Zuckerberg to brainstorm the citizen science angle. Then they reached out to Karl Martin BS’91, then the DNR’s forestry and wildlife research chief,
who knew camera prices were dropping and was also thinking about how to use them to improve research techniques. Martin also had access to a rich store of potential volunteers.

With all the ingredients NASA was looking for, the Wisconsin team won a pilot grant to install 80 cameras. It was an opportunity to improve wildlife research and put big data to work in the natural world. It even seemed like a promising tool for youth engagement—a partial antidote to nature deficit disorder. “It’s a very good example of cross-disciplinary, cross-agency teamwork,” says Martin, now the interim dean and director for UW–Extension Cooperative Extension. “This is how you leverage the Wisconsin Idea.”

Almost as soon as it began, state budget woes put the project on ice. In a curious twist, a raging national debate over gun control led to record sales of guns and ammunition. These sales are federally taxed, and a portion is returned to the states via the Pittman–Robertson Act for natural resource projects. With a secure funding stream, Snapshot Wisconsin began in earnest.

While the technology has been available for years, the ambitious scale remains a challenge. Educators and tribes can install cameras throughout the state, but cameras for private land are being rolled out gradually. Racine, Vernon and Dodge counties recently joined Iowa, Iron, Jackson, Manitowoc, Sawyer and Waupaca. At last count 417 volunteers were operating 607 cameras that have taken more than 8 million photos.

“The logistics are a big part of it,” says Townsend. “The scale that we’re doing this at has never been done before.” But scale is also the payback. Townsend is interested in phenology—the cycling of the landscape from brown to green and back again. Factors ranging from climate change to land use change can influence phenology. The Snapshot cameras are programmed to take an image at 10:40 a.m. every day, in sync with the satellite, providing a much richer data profile for that precise location.

Meanwhile the motion trap captures the phenological patterns of the animals. “Animals respond differently to their environment,” says Townsend. When they give birth, when and where they feed, when they’re out and about and when they’re in hiding all change, and we understand only a fraction of the whys. Bringing landscape data together with animal data may answer a lot of outstanding questions.

“Wildlife research every now and then gets transformed by technology,” notes Tim Van Deelen, a professor of forest and wildlife ecology. Radio telemetry revolutionized wildlife study in the ’70s, but it also took a while before researchers were able to put that information to use.

“That’s where we are with camera data,” Van Deelen says. “We’re in that lag phase where we are figuring out how to be efficient with the use of that data. I’m betting that as cool as things are right now, they’re going to get cooler as analytic techniques develop. I think there is a lot of basic biology that is going to come clear because underlying Snapshot Wisconsin is a very robust sampling scheme.”

There are two kinds of Snapshot Wisconsin volunteers. One group maintains cameras—either on their own land or special project cameras on public lands. Sited away from human activity and preferably on a game trail, the cameras operate day and night, snapping three photos in quick succession via a motion trigger. Memory cards and batteries need to be changed at least every three months, and the card uploaded back to Snapshot Wisconsin. Here technology takes over. To avoid any possibility of surveillance, the images on the card are encrypted. After decoding they are uploaded to Microsoft Cognitive Services, where special software removes images that contain humans. Then the image batches are sent back to each camera volunteer, who removes any people pictures the software may have missed.

After this double-check, the images move to me in my armchair via Zooniverse, a citizen science web platform designed by the Adler Planetarium in Chicago. Its goal is to harness our digital enthusiasm for something more than selfies and cat videos. On Zooniverse you can help with research projects that range from finding evidence of water on Mars to transcribing Civil War telegrams.

Why not just let a computer do it? Even in this age of the Watson cognitive computing platform and pervasive facial recognition, the human mind is still the most agile tool available for subtle pattern recognition. “There is no machine that’s as good as the human brain when it comes to being able to capture these kinds of images and classify them appropriately,” explains Zuckerberg.

Log on to Zooniverse and you’ll soon begin to appreciate both the challenge and your gift. The three-photo sequence captures movement. Some images are empty, and if the frame sways, you can tell that wind triggered the snap. But then you find an empty image where just a tiny bit of vegetation moves, and you realize that something has just passed by. Sometimes there’s just a blur of color, or—at night—eye gleam. After a while, you begin to recognize places and patterns, to appreciate the different ways that animals use and move across the landscape. Even the boring photos can surprise you. There is one squirrel in Sawyer County who loves to run a steeplechase along a few fallen birch logs. Occasionally this camera catches a deer. But just as I was getting frustrated with what felt like the 99th photo of the same squirrel, I realized the field beyond was crowded with 14 young turkeys.

Citizen science dates back at least as far as the then-nascent Audubon Society’s first Christmas bird count in 1900. (Plain folk have been collecting astronomical and meteorological observations for far longer.) In Wisconsin, thousands participate in all kinds of projects, monitoring everything from water quality to bat populations.

Zuckerberg hopes that through Snapshot Wisconsin, biology can join the ranks of such disciplines as meteo- rology that collect data continuously. “Collecting biological data tends to be very difficult,” he explains. State-of-the- art radio tracking can follow only a few individuals. Ecologists want to see how species respond across broad stretches of space and time.

“To me the real value of this is being able to think about animal communities over the course of an entire year,” Zuckerberg says. “It’s thinking about big-pattern ecology.”

Snapshot Wisconsin is in what you might call its giddy start- up phase. There isn’t an end product yet, but as the project ramps up, the anecdotal excitement grows. Director Jennifer Stenglein can tell you that there are quite a few porcupines, not so many striped skunks and a fair number of fly- ing squirrels. Also, that we don’t capture as many wolves as you might think, and that it can be very hard to tell coyotes from wolves. And, to no one’s surprise, there are lots and lots of deer. In fact, 60 percent of the animal photos from Sawyer and Iowa counties have deer. Which leads to an obvious question: Can Snapshot Wisconsin close the persistent (and politically sticky) gap between hunters and the DNR about deer populations? Nobody is taking bets on that, but the project should upgrade research techniques overall. “The way that the DNR tallies wildlife is highly sporadic,” says Townsend. “It’s not systematic, it’s different among different wildlife species, it’s difficult to do and it’s expensive to do well.”

Stenglein’s other major DNR responsibility is care and feeding of the state deer population model, and she sees Snapshot Wisconsin as a dual-use tool. On the one hand, it can contribute to the modeling currently in place, providing an index for population size, some idea of overwinter survival, and the fawn-doe ratio. “Cameras can be the best way to get a couple of those deer metrics, we think,” she says.

“It might also lead to an entirely different way of understanding the deer population,” Stenglein notes. The current model uses data from two observation windows: an August/September survey conducted by the DNR and the public, and the nine-day gun season harvest data. Snapshot would provide many more data points in time.

Two important research projects will help determine the ultimate value of the cameras. Elk reintroduction in Sawyer, Ashland, Bayfield and Jackson counties includes a much higher density of cameras. This will allow scientists to check the validity of the lower-density Snapshot data. And because many of the elk are also collared, traditional telemetry data can also be compared with the camera data. Similar comparisons can be made on another project in Dane, Iowa and Grant counties studying the survival impact of chronic wasting disease. Deer and their predators (coyote and bobcat) are both being collared, and cameras are also planned.

Current deer population models have a strong grasp of general population dynamics, but they are missing crucial landscape factors that we know influence deer. That, says Townsend, is where Snapshot Wisconsin will make the difference. “You are not going to get any one township perfectly, but by sampling enough townships you are going to sample the diversity of land cover and land uses,” he explains.

When all of those cameras meet all of that diversity, patterns will emerge. Find a relationship between deer density and vegetation and you can begin to make predictions. “The strength is in numbers,” Townsend says. “The remote-sensing data is everywhere. Can we harvest all that information to help make the models better?”

Charged with predicting deer populations, Stenglein usually thinks about lots of deer all at once. But as she’s built up Snapshot Wisconsin, a different window on wildlife has opened.

It began when she saw the work of an artist who was using her own trail cam photos for inspiration. Stenglein realized the artist was not painting a generic raccoon, but a very particular raccoon. The artist didn’t “know” the raccoon, and was just looking at photos. Yet there was a kind of individual relationship on view. “I realized that so much of this project is actually about the individuals in these photos,” Stenglein says. “That’s what draws people to this project.”

It was easy to imagine the connection landowners might feel for a camera they install and maintain on their property, or even one on public lands that they use. Stenglein gets lots of email from volunteers thrilled the first time they get a fisher or black bear they didn’t know they had on their property. Sue Steinmann MS’83 volunteered to place a camera on her scrub oak barrens near Arena “to see if we have bear or bobcats,” she says. “I really think we had a wolf come through last winter.” Now she’ll have more than footprints for proof.

Steinmann and her husband are active in ecological restoration, so they are probably more engaged in natural resource issues than most people in Wisconsin. But one of the things being studied by Snapshot Wisconsin is how citizen science can lead to better communication between scientists, resource managers and the public—and how this might lead to better resource management overall.

“When you have folks who are engaged in the process in more depth, and maybe helping to drive some of the questions, or helping to partici- pate in the interpretation of the data, that’s where you’re starting to see some of these community-level outcomes,” says Christine Anhalt-Depies, who is currently pursuing a PhD in wildlife ecology.

Anhalt-Depies is watching the online dynamic among the volunteers— some of whom come from all over the world—and how that evolves. Members of the research team are identified in Zooniverse, and the project also includes a few moderators (you can think of them almost as docents)—volunteers who help new users navigate the learning curve. The chatter is informed and supportive, and while the task might seem rote, it quickly becomes fun.

“I get addicted to doing that and have to stop after a while,” admits Sue Johansen BS’94. As a naturalist at Devil’s Lake State Park, she monitors three cameras for the park and one Snapshot Wisconsin camera in the West Bluff area. While the cameras began as a new way to engage visitors, they’ve also found animals—flying squirrels and short-tailed weasels—that no one knew were in the park. “What happens when you’re not around?” she says. “It’s a different way to connect to the outdoors.”

Then there are the “super users.” Zooniverse projects tend to develop their own core volunteers, people who process fantastically more images than most people. Some of these people are fully vested in the community aspect, engaging in conversation through message boards. Others remain silent. What are they getting from it, Anhalt-Depies wants to know. Will it translate to engagement in the real world?

“These are not cyborgs out there,” Zuckerberg says. “These are people very invested in the research.”

It’s these modern times that make Snapshot Wisconsin so fascinating.

We are becoming so acclimated to screens, to surveillance, to the omnipresence of cameras. Social networks have always mattered, but they are more visible than ever as we attempt to reap their bumper crops and avoid their vicious undertow. Selfies may be changing our very sense of our place in the world. Science and business are being rapidly remade by our ability to collect big data, and by our struggle to understand it.

Snapshot Wisconsin rides the rebounding ripple effects of all of these phenomena. And yet somehow nature remains at the center of the experience.

I admit: I had my doubts. But I threw both hands up in delight when I scored my first black bear. I was tickled to learn the blob that I had thought might be a wounded turkey turned out to be, literally, a happy family pileup of otters. I laughed longer than I should have when the camera caught a coyote leaving a fecal sample. (Photo bomb.)

In nature there is no substitute for observation. And while the parade of images in Snapshot Wisconsin should not be mistaken for being out there, it’s a legitimate supplement, a booster shot against nature deficit disorder.

“If you are going to maintain nature or wild places on this earth as our own numbers grow, I think it’s going to be because we care about it,” says NASA’s Woody Turner. “And to care about something you have to be at least somewhat familiar with it.”

Zuckerberg worries that we are increasingly detached from nature— that some children actually view nature as something to fear. Sometimes he listens to his children, ages 9 and 14, on Zooniverse in the next room. They love all the deer pictures but get totally jazzed by the occasional bear.

“I think using technology to allow another experience is what makes this project fun,” he says. “This offers a window for kids to become interested and engaged in natural history. I think any way you can do that is going to be a positive experience.”

Shaping the Future of Farming

Thirty-five years ago, when CALS bacteriologist Winston Brill and his colleagues set out to exploit science’s newfound ability to manipulate genes to confer new traits on crop plants, the technology was, literally, a shot in the dark.

Working in a facility in Middleton, just west of Madison, Brill and his team blasted plant cells using a gene gun—a device that fired microscopic gold beads laden with DNA.

The idea was to introduce foreign genes that could confer new abilities on the plants that would ultimately be grown from the altered cells. First as Cetus of Madison, Inc., later as Agracetus and still later as a research and development outpost of Monsanto Company, the Middleton lab was, by all accounts, a hub of plant biotechnology innovation.

“Agracetus was the first in the world to engineer soybean, first in the world to engineer cotton, first in the world to field-test a genetically engineered plant,” recalls Brill, who was recruited by Cetus to establish the lab in the early 1980s. “Thus, the Madison area and the UW influence led to historically important events.”

In December 2016, the $10 million,100,000-square-foot facility—a warren of labs, greenhouses and growth chambers—was donated to UW–Madison by Monsanto to become the Wisconsin Crop Innovation Center (WCIC).

The hope, according to agronomy professor Shawn Kaeppler BS’87—now WCIC’s director—is that the center will add to its string of plant biotechnology achievements as one of just a few public facilities in the country dedicated to plant transformation, where genetically modified plant cells are taken from tissue culture and regenerated into large numbers of complete fertile plants.

The advent of the WCIC “is an unprecedented opportunity to add capabilities and capacity we couldn’t afford otherwise,” says Kaeppler, an expert on corn. Its acquisition by UW–Madison, he and others note, comes at an opportune time as powerful new techniques in synthetic biology are poised to make the development of plants with new or improved traits much more than a shot in the dark with a gene gun.

WCIC will function very much like a core facility, providing cell culture, phenotyping and plant transformation services for researchers at UW– Madison and other universities. It is also coming online at a time when the need for such resources is acute.

“There is a recognized need nationally,” explains agronomy professor Heidi Kaeppler BS’87, an expert in plant transformation who is serving as WCIC’s transformation technology director. “There are just a few public facilities around the U.S. and demand is outpacing the abilities of those facilities. It is a bottleneck.”

For researchers like bacteriology and agronomy professor Jean-Michel Ané, a member of the WCIC scientific advisory board, the new center means he will be able to devote more time to exploring such things as the genetic interplay that occurs when plants and bacteria collude to draw nutrients from the air through the act of nitrogen fixation.

Nitrogen-fixing plants such as soybean, alfalfa and clover are staples of modern agriculture. They are essential to the crop rotation practices that prevent exhaustion of soil from crops such as corn. Ané and many other scientists have long dreamed of engineering the ability to fix nitrogen into plants like corn to transcend the need for expensive and environmentally harmful chemical fertilizers.

However, engineering complex traits such as nitrogen fixation in plants that don’t have that innate ability is a monumental scientific and technological undertaking. To begin with, there are two organisms—the plant and a bacterium—working cooperatively. Each has its own genome, and many different genes from each organism are in play to accommodate the act of drawing life-sustaining nutrients from the air.

To confer that trait on corn, for example, is an exercise far more complicated than tinkering with one or a few genes, notes Ané. “The goal is to create maize that has this association. However, modifying a single gene will not be sufficient,” he says. “We modify many genes at a time. There is a lot of trial and error. We need to try many combinations.”

Those combinations come about in the lab as scientists alter individual plant cells by adding or subtracting genes of interest. Today, scientists can harness new techniques such as CRISPR– Cas9—a fast, cheap and accurate genome editing tool—and potent new cloning technologies that allow scientists to easily assemble multiple DNA fragments and their assorted genes into novel sequences.

Even with potent new tools like CRISPR–Cas9, engineering plants is a big, difficult task. A gene needs to be dropped in the right place on the genome and be in association with the right “promoters,” segments of DNA that initiate gene transcription, the first step toward expressing a new gene in an organism. Once plant cells are genetically altered, they must be transformed into large numbers of actual plants for further testing in the lab and, ultimately, the field. It is essential to know, for example, that the new genetic construct is stable, that the new genes are passed from generation to generation, and what effects they may have on plant growth or yield.

The promise of WCIC, Ané believes, will be the opportunity to work through all of those steps more efficiently and cost-effectively, and carry projects from the lab to the field much faster.

“We can focus on really doing science instead of growing plants,” Ané says. “We can now make genetic constructs very quickly. Within a month we can make hundreds of constructs. The limiting aspect is plant transformation. However, the scale of transformation we can do at WCIC allows us to think seriously about applying synthetic biology to plants.”

To begin with, WCIC is providing plant transformation services for corn, soybean and sorghum, big commercially important crop species. But Shawn Kaeppler envisions WCIC playing a role, as well, with crop plants that have not yet risen to the top of commercial research agendas.

To date, commercial interest has focused primarily on just a handful of traits—insect and herbicide resistance—in a handful of widely planted crops. Uncharted territory, Kaeppler says, exists in the full range of crop plants and their many different traits.

A ready example is switchgrass, a native perennial that is under the microscope at the Great Lakes Bioenergy Research Center (GLBRC), a U.S. Department of Energy- funded multi-institutional research center headquartered on the UW–Madison campus. The grass is seen as a potential feedstock for converting its biomass to liquid fuel. However, efficient conversion of plant materials to energy remains a challenge, and plant genetics will play a big role in refining the traits that will make that possible.

“WCIC will help lead us to the next generation of crop breeding and plant genetics,” explains Kate VandenBosch, the dean of CALS, referencing, broadly, the genetic makeup of the crop plants in play. “Scientific agencies at the federal level have invested a lot in understanding genomes, but we still have a lot of work to do to understand how those genes function.”

Indeed, genetic sequencing technologies have advanced to the point where new plant genomes are sequenced with increasing regularity. The genomes of crop plants like watermelon, cucumber, potato, soybean, wheat, corn and many others have been sequenced, but as VandenBosch notes, exploring those sequences to identify the genes that govern plant traits is an unexplored frontier.

Shawn Kaeppler’s own research, for example, is a window to both the complexity and opportunity that lurk in the genomes of plants. One of his interests is the complex of genes—involving anywhere from tens to hundreds of genes—that governs the root architecture of corn. Knowing more about the combination of genes that directs the plant to send shoots into the soil, it might one day be possible to engineer a plant that can send its roots deeper into the earth, providing farmers with a hedge against drought.

“Fifty to 70 percent of all maize genes are expressed in roots,” Kaeppler says. “Some control processes in all parts of a plant, and some specifically control root development and response to environmental stimuli.”

A gene of interest for Kaeppler and his team is one that influences root angle. “Altering root angle even five to 10 degrees can dramatically increase the rate that roots get deep in the soil,” as well as how much root biomass a plant lays down at depth, he explains.

Identifying those candidate genes and mutations of those genes means they can be selected and manipulated in the laboratory to generate plants with different root structures. At WCIC, those plants can be grown in quantity, their new qualities studied and, if promising, tested in the field. The goal, of course, is to provide a practical outcome that is useful to growers.

In plant science, numbers matter. The more plants you can grow to test a new genetic combination, the better, as there are so many variables in play.

“In many aspects of science, doing things on a large scale is critical,” says biochemistry professor Rick Amasino, an expert on flowering in plants. “To have WCIC in our capability is great. Large-scale transformation opens up a lot of possibilities.”

Amasino, who is also a member of WCIC’s scientific advisory board, views the center as an important new national resource. Individual labs, he explains, do not have the same capacity.

“This has the potential to be on a scale greater than any other university’s,” Amasino says. “Individual labs can’t generate the hundreds or thousands of transgenic plants needed to fully test certain hypotheses. Labs around the country and, hopefully, around the world can now do experiments they couldn’t otherwise do. There are so many opportunities out there.”

A Facility With Deep CALS Roots

The name is new, but the Wisconsin Crop Innovation Center (WCIC) holds a prominent place in the young history of agricultural biotechnology. The facility also has long and deep ties to CALS researchers and alumni.

Originally known as Cetus of Madison, Inc., the Middleton facility—owned by
the Cetus Corporation of Emeryville, California—opened in 1981 under the direction of CALS bacteriology professor Winston Brill. The Wisconsin Alumni Research Foundation (WARF) played a key funding role in the early days of the company.

Cetus of Madison, Inc. initially focused on evaluating and testing a wide variety of natural rhizobia species to better understand their role in nitrogen fixation and nodulation in legumes, with the hope of someday enabling maize to have that capacity.

As interest in biotechnology grew in the early 1980s, the facility’s focus changed to inventing and innovating ways to introduce genes into plants. In 1984, Cetus Corp. sold half of its interest in Cetus of Madison, Inc. to the WR Grace Co.—and thus the company name “Agracetus” was born.

Great discoveries followed. An electric “gene gun” and transformation methods developed at Agracetus revolutionized the plant transformation process. Many plant species were subsequently transformed, including tobacco, peanut, sunflower, soybean, maize, cotton, cranberry, canola, poplar, wheat and rice. CALS researchers Kenneth Raffa, Brent McCown PhD’69 and Elden Stang, as well as WCIC associate director Michael Petersen BS’87 (then still an undergraduate) and Richard Heinzen MS’74, collaborated with Agracetus scientists during that period. But that wasn’t the only significant research taking place. Other studies critical to agricultural improvement focused on cotton fiber quality, transformation process improvements, polymerase chain reaction (PCR) method development, insect and disease resistance and herbicide tolerance. A number of CALS faculty, including Michael Sussman, Richard Amasino and Andrew Bent, were highly involved in consulting with Agracetus in many of these areas.

In 1990, WR Grace Co. acquired full ownership of Agracetus. During the early 1990s, Agracetus ventured into research in DNA vaccines—using an improved “gene gun”—and contracted plant transformation services to others within the industry, including, most notably, the Monsanto Company. Collaborating with biological systems engineering professor Richard Straub PhD’80 (now CALS senior associate dean) and other CALS researchers, the company also worked on producing industrial enzymes in plants.

After successfully generating plants that eventually became commercial products
for Monsanto, including Roundup Ready Soybeans and Bollgard Cotton, the facility was acquired by Monsanto in 1996.

Over the next 20 years, Monsanto used the facility as its primary site for soybean and cotton transformation. Other R&D at the site included corn, canola, wheat, rice and alfalfa transformation, gene expression, molecular testing and seed chipping/genotyping.

The site was considered a “center of excellence” for Monsanto due to its highly innovative employees, high throughput transformation capabilities and ability to consistently perform above and beyond expectations.

In July of 2016, Monsanto relocated a number of remote functions back to its St. Louis headquarters in the interest of business consolidation. In the hope that the Middleton facility would continue to work toward the betterment of agriculture, Monsanto the following December donated it to longtime collaborator the University of Wisconsin– Madison, along with University Research Park.

Not surprisingly, given the long history of CALS involvement, agronomy professor Shawn Kaeppler BS’87 was chosen to serve as facility director.

A Tale of Two Cheeses

Many of the world’s greatest cheeses are made in Wisconsin. It’s a fact that begs the question: How do those cheeses get to be great?

A key ingredient is the Center for Dairy Research (CDR), based at CALS and operated with funds from dairy farmers, dairy food manufacturers and processors, and other industry partners. Located within a licensed, operating dairy plant on the UW–Madison campus, its facilities include a cheese pilot plant, a dairy ingredients pilot plant, a sensory lab, an analytical lab and an applications lab, all of which are available to cheesemakers and other dairy manufacturers for trial runs and testing new products. For experienced cheesemakers seeking rigorous additional training, CDR, in partnership with the Wisconsin Milk Marketing Board, offers a three-year program of courses and mentoring leading to certification as a Wisconsin Master Cheesemaker.

CDR’s experts boast hundreds of years of combined experience in industry and academia. Those experts have something else in common: Many grew up in the same milieu as the cheesemakers they work with around the state.

We are pleased to present here the success stories of two very different kinds of Wisconsin cheesemakers who availed themselves of CDR’s support and expertise.

Mexican Melty 

When milk is converted into cheese, science alone takes you only so far, says Tom Dahmen, a second-generation cheesemaker who manages the Chula Vista cheese factory near Browntown, in southwestern Wisconsin.

“I’m a big believer in heavy-duty science, but there is always a bit of magic in making cheese,” says Dahmen, who began washing cheesecloths at age 6. Intuition and experience also play a role, he notes.

At Chula Vista, those ingredients are combined to produce a string cheese called Oaxaca (wa-HA-ka), which received the Best in Class award in the Hispanic melting cheese category at the 2016 World Championship Cheese Contest in Madison. The CALS com- munity can take pride in this honor, because CDR helped Chula Vista create the cheese.

Oaxaca is a white, mild-flavored cheese used in many Mexican dishes. The cheese gets its name from the Mexican state where the style originated.

At the Chula Vista plant, named for its beautiful view of Lafayette County dairy farms, people work two shifts making two styles of Mexican cheese.

Chula Vista and V&V Supremo of Chicago were cheesemaking partners for decades. Last September V&V bought the plant, where employment has risen to 80, up from 34 about seven years ago.

Although Chula Vista purchased and sold Oaxaca cheese for several years, “We were never happy with the qual- ity, so we decided to move production in-house,” Dahmen says. “I had spent 14 years making a related style, but there were challenges to our ‘make,’ so we went to CDR. They helped us from the beginning.”

Starting in around 2010, Dahmen and Alan Hamann, V&V’s senior man- ager of quality control, began talking with CDR researchers about the details of fat-protein ratios, milk solids, chemis- try and pH.

“You have to control all of these factors even as the milk changes subtly from one truckload to the next,” says Hamann, who has more than 36 years of experience in the dairy industry.

Once the ideas were collated, they needed to be tested. At Browntown, each test would require 5,000 pounds of milk, Hamann says. Vats at CDR, however, would require only 500 pounds, reducing cost and eliminating errors attributable to running tests with different batches of milk. “At CDR, we could test several variables at once,” Hamann says. “Working at CDR drastically cuts your timeline and offers much more control.”

When the improved Oaxaca reached the market in 2015, Chula Vista was producing one or two vats per week. Now the company makes that much in a day.

Oaxaca cheese is produced using a procedure similar to that used for fresh mozzarella. Pasteurized milk is set (coagulated) and cut in a stainless- steel vat and then turned into curd slabs that are moved to a cooker-stretcher, a machine where heating and repeated folding links protein molecules, forming the familiar elastic product called string cheese.

The stretched curd is then formed into cylinders by six nozzles, cut to length and packaged for shipment to stores ranging from “mom and pops” to Wal-Mart, says Philip Villasenor, V&V’s vice president of manufacturing.

Beyond technical advice, CDR offers business consulting to the dairy industry, says Vic Grassman, CDR’s technology commercialization manager. “We help firms develop products and expand,” says Grassman. “I help with economic development financing, permits, workforce information and development.”

As employment tightens, particularly in rural areas, CDR links manufacturers with existing resources for economic development. “It’s not just ‘Develop the product and you are on your own,’” Grassman says.

But when you visit Chula Vista, it’s all about the cheese. Even though Chula Vista aims for a standardized, pure product, “Every vat is a controlled experiment,” says Dahmen. “We are predicting what is going to happen, and we are pretty accurate, but this is a living system, and unplanned things happen: A pump dies. A cooler dies. People don’t show up. But once you start a batch, you have to finish.”

Those snafus are familiar to both Chula Vista and CDR, says Dahmen. “The beauty of working with CDR is that they are heavy, heavy on science, but their people have all worked in the industry. They have this blend of science and art that you can only gain from experience. For our Oaxaca cheese, they greatly shortened the timeline to reach the product quality we were looking for.”

The collaboration with CDR also served as a rich educational experi- ence for Dahmen. Earlier this year he earned certification as a Wisconsin Master Cheesemaker for Quesadilla and Oaxaca cheeses.

Alpine Goodness

If you walk into Roelli Cheese Haus near Shullsburg in southwest Wisconsin, you’ll see plenty of succu- lent Wisconsin cheeses—but not Little Mountain, the company’s champion cheese. It lives behind the counter, with nary a sign.

Little Mountain, described by its maker as a “classic upland style from Switzerland,” is not contraband, but Roelli is practically running on empty after a “Best of Show” at the American Cheese Society contest last July. “We feel pretty honored,” says company owner Chris Roelli, noting that Little Mountain bested 1,842 other cheeses in the competition.

Although Roelli is a fourth-generation cheesemaker, in creating the recipe and honing the details of microbiology, timing and equipment, he got assistance from CDR. “For us as a small business, tapping the experience at CDR was invaluable,” says Roelli. “It accelerated our path to bring this cheese to the market, literally by years.”

Little Mountain requires at least seven months of careful aging to achieve its characteristic flavor, texture and rind. Aging occurs in an above-ground “cellar,” with cooling pipes along the walls. Forced air would waft microbes, threatening the cheese with spoilage.

Roelli’s great-grandfather, Adolph Roelli, immigrated from Altburon, Switzerland to Green County in the early 1900s. “He was a cheesemaker’s apprentice in different areas of the Swiss Alps,” says Roelli. “He settled here as a farmer and sold milk to a co-op, which offered him a job as head cheesemaker, based on his experience in Switzerland.”

Roelli says he’s been in and out of cheese factories all his life. “I watched my granddad make commodity cheddar,” says Roelli, but the factory closed shortly after Roelli got a cheesemaker’s license in 1989. “We weren’t able to compete.”

In 2005, unable to stay away from the family business, Roelli returned with “Cheese on Wheels,” a cheese plant mounted on an 18-wheeler.

The following year he started an artisanal cheese business in a new factory behind his store on Highway 11 east of Shullsburg, and started to envision a Swiss cheese that would go back to the family’s roots. In preparation, he says, “I went around and tasted as much Swiss mountain-style cheese as I could.”

Both Emmentaler and Gruyère were already produced nearby, and Roelli mulled a Swiss version of Parmesan before settling on an Appenzeller, a hard-rind cheese flavored with “washes” of brine as it ages.

He approached John Jaeggi, CDR’s cheese industry and applications coordinator, with some flavor profiles he was looking for. “I made a couple of batches here as total experiments, and we went to the CDR and made six batches to fine-tune the culture and process,” Roelli says.

In Jaeggi, Roelli found a particularly kindred spirit for this project. Jaeggi is a third-generation, Swiss-descended cheesemaker from Green County who, like Roelli, grew up in a cheese family. “If you look at the history of Wisconsin, a lot of cheese factories were family operations and the family was involved in all aspects of the business,” Jaeggi says. “The younger generation would start on the bottom floor, cleaning, sanitizing, packaging and working their way up.”

The initial conversations with Roelli, Jaeggi says, concerned flavor, texture and equipment. “We talked about aging, culture, the ‘make’ schedule. Chris came up to CDR and worked in our test vats, looking at cocktails of microbial cultures for different flavor profiles. Once we got close, we went to his plant two or three times to make the cheese, then optimized the make procedure to fit his plant.”

The cheese would be aged from seven to 16 months while being washed with a hush-hush recipe of salt, yeast and bacteria. The wash would break down proteins and fat to create the rind and desired flavor.

“Although artisan cheesemakers are pretty open in general, when it comes to world-class cheese, there are still secrets out there,” Roelli says.

Holding secrets is a point of pride at CDR. “To be able to draw from the knowledge base at CDR was invaluable,” says Roelli, who has earned certification as a Wisconsin Master Cheesemaker. “There is nowhere else you could get that. If John Jaeggi or Mark Johnson [a CDR cheese scientist] asks for help from someone in Europe, they will help. They don’t know me, but they know them.”

Someday the world’s top cheesemakers may start to know Chris Roelli, who has built his future atop his history and the cheese wisdom brought by his great- grandfather from Switzerland. “If you make something really good, people will find it,” Roelli says. “We entered competitions to garner some interest from places where we don’t normally get it. You don’t have to set the world on fire with advertising.”

Between the store and the cheese plant, Roelli Cheese Haus has five employees. Chris Roelli also runs a larger business hauling milk from farms.

Demand for Little Mountain exploded after the award in July, Roelli says. “We beat the world champ from last year, and three other American Cheese Society Best of Shows from past years. We have upped production for the end of 2017 as much as we can. I still have a list as long as my right arm wanting the next batch.”

Lactation Sensation

WHEN THE CITY GIRL decides to study lactation, she must first learn to milk a cow. Laura Hernandez, an assistant professor of dairy science at CALS, remembers that lesson.

Her tutor that day was Jessica Cederquist, then a fellow grad student and now CALS herd manager. “People who have never milked are used to what you see in the movies,” Cederquist explains. You know the choreography: grab a teat, pull down, milk squirts into the bucket. But that technique simply squeezes milk back into the udder. And just about everybody makes the mistake. “It is a rite of passage to stand back and laugh,” she admits.

“She thought it was very funny,” Hernandez recalls. “I think that was the beginning of a very good friendship.”

The milking got a little crazier once Hernandez ramped up her inquiries into how lactation works. Her first experiments required milking two halves of the same cow, comparing milk production. Because she was pairing the front right with the back left and vice versa, she had to replumb two half milkers, using a surplus of hoses and buckets. She’d also recently had knee surgery.

“You’re already kind of crowded in there and now you’ve got her fancy contraption and all of her buckets and a big old knee brace,” says Cederquist. And it’s a waterbed stall, so every time anybody moves, the floor moves, and the buckets yaw precariously. “She’s darn near laying on the floor under the cow, trying to figure out how she’s going to get this thing to stay on.”

Hernandez is still making things unusual for Cederquist. Lactation is a delicate enough phenomenon that the typical dairy farmer puts animals who are in the late stages of pregnancy on vacation. This is exactly when Hernandez needs to poke and prod, monitor and manipulate.

The hassle seems worth the reward: Her exploration of the role of serotonin in lactation has the potential to significantly improve animal health and boost milk production. There may also be profound lessons about the role of serotonin in human health. While seratonin was once considered the miracle molecule of mental health, Hernandez is helping unravel its role in many more parts of the body.

“There is still an infinite box of things it probably does that we can’t understand,” says Hernandez. Which is all the more interesting because it’s such a simple molecule, just a modified amino acid. It’s as if a Lego block were able to control a nuclear reactor. “I really am just completely fascinated by how a modified amino acid can regulate what feels like the universe at times,” Hernandez says.

On the road between Hernandez’s hometown of El Paso, Texas, and the New Mexico State University campus in Las Cruces, a line of dairy farms stretches across the landscape. Despite her urban upbringing, the cows fascinated her. “As an athlete I was like: how does she do that?” recalls Hernandez, then a scholarship swimmer. “I just thought they were really cool animals, what they could do from a biological standpoint.”

Drawn to biology, Hernandez chose animal science over straight biology because she was more interested in working with mammals than with crabs and nematodes. But her real immersion didn’t begin until her senior year, when she transferred to New Mexico State from Iowa State University. In Ames her swimming schedule had kept her out of the lab, but that changed when she got to Las Cruces.

“I loved working in the lab,” says Hernandez. “That was where I found my home.” When she couldn’t decide between professional schools, she continued at New Mexico State to earn a master’s degree in animal science and toxicology.

In 2005 she started her doctorate at the University of Arizona with Bob Collier, a physiologist in the dairy sciences. He was interested in how genes interacted with the environment, and lactation was the ideal process to study: genetically programmed, but initiated and controlled by changes in the environment of the cow.

The year before Hernandez arrived, the small world of lactation science had been upended by the unexpected discovery that serotonin, long considered simply a neurotransmitter, also had a role in regulating lactation. Collier reached out to Nelson Horseman at the University of Cincinnati, where the discovery had been made. Horseman studied breast development, but his central interest was breast cancer. Collier offered his dairy expertise and suggested that they collaborate on expanding this discovery from the mouse to the cow.

Hernandez undertook the research for her dissertation, supervising many of the active experiments. Deeper she went, her work encompassing an intense collaboration into the complex molecular underpinnings of milk production.

After finishing her Ph.D. she began a postdoc in Horseman’s lab. One day in Cincinnati, Gerard Karsenty, a geneticist visiting from Columbia University, presented his research involving gut serotonin, calcium and bone mass. Afterward Hernandez turned to Horseman and wondered aloud: If gut serotonin had a role in bone mass, could this also help explain its role in lactation?

Nursing typically requires more calcium than diet alone can provide, and the difference comes from the mother’s bone. A nursing mouse will lose up to 20 percent of bone mass in 21 days. Human mothers can lose 6 to 10 percent of their bone mass over six months. Studies in West Africa and Korea suggest that the longer a woman breast-feeds, the lower her bone density.

It’s not surprising that serotonin might have more than one role in the body. Along with dopamine it’s the oldest known hormone, and nature loves to reuse its creations. In fact, serotonin first evolved in plants. Plants have no nervous system, so it couldn’t have been a neurotransmitter. How a simple molecule engages in complex processes is by acting as a molecular key in many different cellular locks. Scientists have now identified 20 different serotonin receptors. The mammary gland alone has five.

So how to uncover serotonin’s role in withdrawing calcium from bone? Scouring some old genetic assays, Hernandez found a likely ally: parathyroid hormone-related protein (or PTHrP). Her initial tests were so strong that she suspected her equipment was off.

But further experiments confirmed that serotonin was causing an increase in PTHrP in the mammary gland during lactation. This, in turn, was a key signal liberating calcium from bone for the mammary glands.

Hernandez’s research portfolio made her an obvious match when a position opened at CALS. As a newly hired professor in 2011, her first question was obvious: Could she leverage our knowledge of PTHrP in the dairy cow?

Lactation is hard, and one of the biggest problems faced by dairy farmers is the “transition cow,” a cow in the three weeks before and after calving. Between the physiologic stress of birth and the metabolic stress of commencing lactation, for the first 20 to 30 days of lactation the cow is expending more energy than she can take in.

Calcium complicates things, as it takes a couple of days to activate the mechanism that borrows from the bone. Sometimes that leads to a calcium deficit—or hypocalcemia, also knownas milk fever. Because calcium is critical for biological functions, assisting with everything from muscle contraction to immune function, a shortage can lead to a variety of potential health problems including ketosis, displaced abomasum and retained placenta. Gut issues can arise because the intestines aren’t contracting. Reduced immune function leaves the cows more susceptible to mastitis.

“That’s a precarious time frame for them,” Hernandez says. “If you have a calcium problem, other issues compound.”

It’s a daily concern for dairy farms. Even on a very good farm, 3 to 5 percent of the animals are going to wind up with milk fever. Scaled up to a 10,000-herd farm, that means one or two affected cows every day.

“Not every farmer is going to automatically relate to Hernandez’s deep molecular work,” says herd manager Jessica Cederquist. But put it in terms of milk fever and the transition cow, and “every dairy farmer on the planet knows what that means,” she says.

With startup money tight and a big idea, Hernandez developed an ambitious research agenda. She found a collaborator in Jimena Laporta, a graduate student fresh from Uruguay. Laporta read the plan and committed the very next day. “We were throwing all of the chips on the table and hoping for a win,” says Hernandez.

The idea was simple: Could you boost PTHrP levels with nutritional supplements? They fed rats two amino acids—5-hydroxytryptophan (abbreviated as 5-HTP) and straight tryptophan. Both are chemical precursors in the synthesis of serotonin.

They began with rats, and feeding was the easy part. The hard part? They also had to milk them. Forty-five rats. Every day. How do you milk a rat?

After knocking it out with sleeping gas, you inject a minute quantity of the hormone oxytocin. A small suction device evacuates the teats; each animal has 10. It was a time-consuming, two-person job. Hernandez and Laporta sacrificed weekends and postponed professional travel. Eventually they got the process down to about an hour and a half.

The 5-HTP worked. Then they confirmed that it works in the cow via IV infusion. Now the lab is working on developing a cow feed that accomplishes the same thing.

Meanwhile, on the molecular level they were focusing on how the serotonin was actually affecting the mammary gland and how it translated into the chemical signals that drive bone resorption. In addition to the PTHrP they identified a gene—already nicknamed sonic hedgehog—as another link in the chain in collaboration with researchers Chad Vezina and Robert Lipinski at the UW–Madison School of Veterinary Medicine.

“It’s a very big picture of a very small molecule,” says Laporta, now teaching at the University of Florida. “Nobody knew that serotonin could do all these things. I think we opened a black box.”

Repeat: lactation is hard. Hernandez became a mother in the first year of her professorship, and nursing was as fulfilling as it was excruciating. She was lactating, she was teaching about lactation, she was manipulating lactation. Under the grueling stress of a new research program she took only nine days of maternity leave.

One day in mid-February her husband came home to find Hernandez crying on the bathroom floor. She couldn’t find time to pump, and her hair was falling out. He suggested it might be time to stop nursing. She’d made it seven months under a colossal workload. They still had some milk stored to facilitate transition to the bottle. “But I want to make it a year,” Hernandez objected. “I’m a lactation biologist! I must!”

“It was so hard,” she reiterates. “It’s made me even more of an advocate for helping women after they give birth. That’s where my biggest interest is: The mother’s ability to deal with lactation and to do so healthily for herself while also taking care of her baby.”

And so Hernandez has forged into human health. As the role of serotonin beyond brain chemistry continues to unfold, obvious questions arise. Selective serotonin reuptake inhibitors, or SSRIs, now dominate the antidepressant market and include such household names as Prozac, Paxil and Zoloft. Among their side effects is a decrease in bone density. Nursing also decreases bone density. With 12 percent of pregnant women taking SSRIs, does the combination of SSRIs and nursing set these women up for severe bone health issues later in life?

Most studies that looked at nursing and SSRIs focused on the infant. “Almost nothing out there looks at the long-term implications for the mother,” reports Sam Weaver, a third-year Ph.D. student in Hernandez’s lab. Weaver began as an undergraduate in the lab, assisting Laporta with her milking. Now Weaver supervises her own mouse dairy as she tries to untangle the precise impact of SSRIs on lactation and the health of the mother.

Weaver harvests more than milk. The mice are dissected with precise determination as blood, mammary glands, kidneys, intestines and bone tissue are examined for health and their reactivity to serotonin. Their femur bones are sent off to a collaborator in Boston for specialized imaging.

“Can we somehow help women breast-feed but also stay on their medication, and help them avoid some of these long-term bone issues?” asks Hernandez. She hopes to begin working with human populations soon.

Now that the lab has characterized the complexity of serotonin in lactation, the team is trying to get a handle on its role as one of the body’s master regulators. Only about 2 percent of serotonin actually resides in the brain; the vast majority circulates throughout the rest of the body. “We’re finding it popping up in all sorts of places,” says Weaver.

A newer project is working on yet another serotonin-lactation connection. Obese women tend to have higher serotonin levels—and they also have a harder time initiating nursing. This suggests yet another crucial role for serotonin as a regulator of energy balance in the body. By unlocking its role, they hope to find a way to make nursing easier for these mothers.

The legacy of Wisconsin is so milk-soaked it can be hard to remember that lactation still holds mystery and marvel. It’s a unique biological process that has given up its secrets slowly, and there is still much to learn. Experiments with a wide variety of mammals have shown that as long as you keep removing milk, the gland will keep making it.

Though she’s unlocked some of the secrets behind this apparent superpower, Hernandez remains entranced: “It just fascinates me that it can continue to do that.”

It’s not a stretch to call lactation one of the more significant developments in the evolution of life on this planet. The expanded ability to feed our young has allowed mammals to adapt to a wide array of variations in our environment. “Keep the baby alive,” says Hernandez. “I think it ties back to that, making us better mothers.” Our human accomplishments are stamped with an indelible mammalian signature.

Hernandez’s peculiar dairy, with its few hundred mice and few dozen patient cows, keeps producing under the labors of a handful of motivated students. “Sometimes it’s overwhelming, and it feels like we’re not getting anywhere and we’re not going to get anywhere,” Hernandez says. “Because with every answer comes another question.”

Even as she continues her fine-scale investigations, Hernandez hopes that young farmers can go back to their dairies and incorporate some wonder into our conversations about animal agriculture.

As Hernandez and dairy farmers know, when it comes to a cow’s well-being, milk is a marker.

“If cows are not being fed properly, or taken care of properly or housed properly, they are not going to make a lot of milk,” Hernandez says. “That’s a basic mammalian response. That should tell you something about the welfare of the animals.”

Students on the Cutting Edge

CALS undergrads are an impressive bunch, eager to get the most out of their time at college. As they tackle the challenging coursework required for their degrees, many also pursue research and internship experiences to augment their education—and help prepare them for their future careers.

Such experiences can be found on campus and off, with companies, nonprofits and governmental agencies. Some are summer gigs, others run year-round. The work students perform in these roles is as diverse as the disciplines that CALS covers: basic biological research, crop management trials, marketing campaigns, food product development, nutrition-focused meal planning and so much more.

“These experiences are important because they allow students to test-drive potential career paths, to get a true sense of what they would be doing in a job setting, which in many cases can’t be grasped from what they learn in the classroom or read in a book,” says entomologist Rick Lindroth, until recently associate dean for research at CALS.

They also help CALS students stand out in competitive environments. “When organizations review candidates for jobs and graduate school applications, it’s the transferable skills gained from research labs, internships and similar experiences that set students apart from each other,” says Megan O’Rourke of CALS Career Services.

CALS prides itself on being a great college for such experiences, a place where researchers are eager to have undergrads come work in their labs. CALS Career Services maintains strong connections with state and national organizations looking for talent and helps place students in internships—and jobs.

At the most recent UW–Madison Fall Career Fair, there were more than 110 organizations recruiting students from CALS disciplines, notes O’Rourke.

For researchers and organizations that hire CALS student researchers and interns, there are a number of benefits from investing in young scientists and professionals.

According to Lindroth, who has had a number of undergrads in his lab over the years, they help move projects forward, including some that might not otherwise get done. “And they bring a level of energy, enthusiasm and wonder that is refreshing,” he notes.

To illustrate the benefits of these experiences for students, mentors and organizations alike, here are some recent research and internship experiences of six CALS students.

Name that plant!

Thanks largely to the efforts of Saige Henkel, visitors to Allen Centennial Garden who ask themselves “I wonder what plant this is?” have a new way to find out.

Allen Centennial Garden is a gem on the CALS campus, a resource for students, area horticulturalists and home gardeners alike. The 2.5-acre garden features 21 mini-gardens, from English to rock to native Wisconsin, showcasing more than 1,000 kinds of plants. It’s no wonder that most visitors need some help in identifying them.

Henkel, a junior majoring in landscape architecture, led the effort to assemble the garden’s new Online Plant Database, an interactive public platform where students and community members can search through the garden’s entire plant collection and find photos and key information about the plants.

“People can use specific filters to find exactly which plant they are looking for. It’s a great tool for when you’re in the garden on the weekend and staff aren’t around to identify plants for you,” says Henkel, who created more than 800 of the database’s 1,100 entries so far.

Henkel started interning at Allen Garden in spring 2015. Her career plan involves joining a landscape architecture firm—preferably one that specializes in planting design and sustainable urban development—where she will likely spend most of her time in front of a computer doing design work. Prior to this, however, she knew she wanted some kind of practical horticultural work experience.

“I wanted to get my hands dirty and learn more about the physical maintenance of the plants I’d be putting in my designs,” says Henkel.

Allen Garden provides a number of opportunities for undergrads to have meaningful experiences. When garden director Ben Futa joined the garden in 2015, he created six year-round “student director” positions.

“Student directors take an active role in everything we do, from planning public programs to envisioning new horticultural displays. This real-world experience is preparing them for success in a competitive job market,” says Futa.

Henkel was in the first cohort of students that Futa hired. She’s had a number of different responsibilities at the garden since she joined, including leading a major garden design project. She developed a design for a new bulb lawn in the English garden—and then got to plant it and see it bloom last spring.

“I’ve definitely beefed up my horticultural knowledge, which was my original goal in applying for this internship,” notes Henkel. “Working here, I’ve also started to realize that landscape architects work on a variety of projects, from hardscape plazas to public garden spaces, and it’s really shown me the variety of possibilities that I’ll have with my degree.”

Two ways to publish

Eddie Ruiz is a go-getter. As a freshman, he took a student employee position in the lab of Dr. Timothy Kamp, a cardiology professor and stem cell researcher. He started out maintaining equipment and cell lines. Over time, as Ruiz learned more about the lab’s research program, he started contributing to various research projects, including helping to develop a protocol to produce a special type of heart cell, called a cardiac fibroblast, from human pluripotent stem cells.

Ruiz, a genetics major, quickly realized he’s not the only undergrad doing meaningful research on campus, with significant results to share. In fall 2015, he teamed up with Stephanie Seymour, a molecular biology and economics double major, to give more undergrads an opportunity to go through the publication process and share their findings. The duo founded the Journal of Undergraduate Science and Technology (JUST). Student research journals are already popular at other research universities such as Caltech, Harvard and the University of Texas at Austin.

“People tend to think undergrads are working on small parts of a research project. While this is definitely true, there are also many students like Stephanie and me who are working independently on research projects that justify greater attention,” says Ruiz.

Ruiz and Seymour, serving as coeditors-in-chief, assembled a team of 30 undergrad volunteers to put together the journal. Ruiz calls it “an incredibly challenging yet rewarding leadership experience.” The group tackled—from scratch—the tasks of careful review of scientific research, editing, design, marketing and publication production. The first issue came out in May 2016, while the second appeared in December.

“JUST has given our editors—who are all UW–Madison undergrads—a unique opportunity to learn how to dissect and critique an array of scientific manuscripts. JUST has trained undergraduates how to peer-review scientific papers and enabled students who are passionate about art and science to explore this intersection through the design of our publication and website,” says Ruiz. JUST’s website, justjournal. org, which houses its online publications, has been visited more than 10,000 times in the one year since its creation.

And JUST is not the only publication experience Ruiz will have during his time at CALS. After attending a scientific talk with fellow members of Tim Kamp’s lab, Ruiz came up with a research idea and took it to Kamp.

“His research project was largely motivated by a seminar in which he learned about 2-photon microscopy and its application to biological research,” says Kamp. “He knew the questions we were investigating in the lab and thought this technique could help us understand the matrix proteins that cardiac fibroblasts generate.”

Kamp’s group is in the process of preparing a scientific paper describing this project. Ruiz, now a senior, will be a co-author.

“It has been wonderful to see him master this somewhat challenging methodology and optimize data analysis,” says Kamp. “Eddie is an undergraduate driven to explore and understand, which will serve him very well in a future career in science.”

Driving Arlington ARS toward precision ag

Ryan Seffinga spent a good part of last summer in an ATV driving around the Arlington Agricultural Research Station. While it may sound like an aimless task, it was actually a key step in Arlington’s ongoing effort to adopt precision agriculture technologies.

Over the course of three weeks, Seffinga BS’16 navigated his souped-up ATV, which was outfitted with a GPS receiver, a cellular modem and a monitor, around each of the station’s 350 research plots, gathering field boundary data to input into the station’s new farm management system—which Seffinga also helped install.

“I helped set up a server at the station’s headquarters and installed a farm management program on it. This program helps automate data collection and makes it easy for those with access to view key data for any given field,” explains Seffinga, who was a summer intern at Arlington last year.

Now, monitors attached to the station’s equipment—including the forage chopper and combine—and located around the grounds can send crop yield, soil moisture and other key data directly into the station’s new program, where staff can assess the information, field by field.

This big project likely wouldn’t have come together last summer without Seffinga’s help, notes his supervisor, Kim Meyers, assistant superintendent at Arlington.

“As with any farm, there is never enough time in the day to get everything done,” says Meyers. “But Ryan got it all set up and got the pieces working together. He was a huge asset.”

Meyers expects big payoffs down the line. “With enough years of data, we can make educated decisions about where our research and management practices should go in the future,” she says.

Seffinga graduated this past December with a bachelor’s degree in biological systems engineering. On campus, he was involved in the American Society of Agricultural and Biological Engineers (ASABE) student organization, ASABE’s collegiate quarter-scale tractor design competition, and the Engineers in Business student organization.

He already has a position with John Deere as a product design engineer for hydraulic excavators, and he hopes to start his own engineering and sales business someday.

Seffinga says his time at Arlington shaped his goals and helped him realize the importance of precision agriculture. “

I now know that the agricultural industry is investing more money into the precision side of things,” he says. “By remaining involved in this part of the industry, I can expect tremendous opportunities to present themselves, especially in new product development.”

Improving food safety

As a freshman, Makala Bach had already figured out that she wanted to be a food science major. Tough decision over, right? Not so much.

“I soon found out that the world of food science is a broad one, and that I would have to narrow down my interests even further—and the Food Research Institute’s summer internship program seemed like the perfect way to do that,” says Bach.

The Food Research Institute (FRI), housed in CALS, is a premier center for the study of microbial foodborne pathogens. Outreach is part of the institute’s mission—helping communities, government agencies and companies identify and resolve food safety issues. Another component of FRI’s mission is education.

“We developed the summer undergraduate research program to provide students, who may or may not have been thinking of careers in the food industry, exposure to important issues in food safety,” says FRI director Chuck Czuprynski, who helped establish the program in 2012.

Participating students work on research projects, discuss food safety topics with campus faculty and take field trips to food processing plants to learn about their challenges.

For her program, Bach worked on a research project sponsored by the Wisconsin Association of Meat Processors with the purpose of helping Wisconsin meat processors improve the safety of their processes and products. With guidance from a number of FRI faculty and staff mentors, including Jeff Sindelar, Andy Milkowksi and Kathy Glass, Bach studied the growth of the foodborne pathogen Staphylococcus aureus on the surface of ham that utilized slow-cooking (aka thermal processing) procedures to assess the risk of toxin production by the bacteria. The results of this study will provide practical solutions for ensuring that slow thermal processing procedures used in many Wisconsin meat products (examples: bone-in hams and summer sausage) won’t result in food safety concerns.

Bach received a lot of guidance at the start. Her mentors helped her set up the experimental design. One of them taught her how to pipette. Another, how to make ham. Before long, however, she was working primarily on her own.

“We work very hard to make sure it’s a good first research experience for our students,” says Sindelar, a CALS professor of animal sciences and UW– Extension meat specialist.

And for Bach, it certainly was.

“During the first week or so, there were days and days of monotonous prep work. Everyone in the lab told me to just wait until I had data—that that’s when the exciting part would begin. And they were right,” says Bach. “There’s nothing more exciting than being able to draw conclusions that might actually have an impact, all based on work you’ve done.”

Bach ended up staying on at FRI working in the applied research lab to help finish the project. The team is planning to publish the results in a peer-reviewed food safety journal.

“Bach’s work will have a practical impact. It affects many meat manufacturers around the state and the nation,” notes Sindelar.

And there’s another positive outcome: Bach is now considering going to graduate school to study food microbiology.

Getting a global perspective

When Abagail Catania, as a freshman, attended a Career Fair run by MANRRS (Minorities in Agriculture, Natural Resources and Related Sciences, a national professional development society), she figured it was too early for her to land an internship. But a John Deere rep encouraged her to apply, and even gave her an hour to polish her resume before conducting an on-thespot interview.

“That employee took a leap of faith and allowed me to fix up my resume, and ultimately I was hired during the second-round interview stage,” says Catania.

That summer, Catania moved to Moline, Illinois to work as a sales and marketing intern for John Deere’s construction and forestry division in order fulfillment and logistics. One of her projects involved assessing the shipment and storage of large machinery being sent to five U.S. ports from Japan. In certain ports, older units were sitting in storage too long, taking up valuable space.

The work involved digging into five years’ worth of pertinent sales data, and, for Catania, it was exciting because it had a clear end goal: to help John Deere improve operations.

“As a student going through classes, we are assigned work with data sets, but we don’t see how it’s applied or how to pull it from an actual database. I was able to do this in my everyday work environment, and I was able to learn a great deal about different ways to analyze data,” says Catania, who is majoring in agricultural business management with a certificate in criminal justice.

The following summer Catania returned to John Deere for a second internship, this time as a global marketing intern with the company’s worldwide customer experience team. This position was perhaps a bit closer to Catania’s heart, as she has a taste for international travel and dreamed of someday working abroad.

The work put her in contact with employees in John Deere’s various foreign offices as she led an effort to revamp the company’s customer experience survey process.

“I had to effectively communicate with key stakeholders from all over the world to ensure they were all aligned on how the survey process should take place,” says Catania.

It was another great experience, one that provided Catania with valuable networking opportunities and solidified her good feelings about the company.

“The intent of our internship programs is to provide meaningful assignments providing value to Deere while giving students valuable real-world experience,” says Gary Hohmann, a manager of outbound logistics and order fulfillment to Brazil. He supervised Catania’s first internship.

“It is great to know that I have people at John Deere who are looking out for me and want to support my career,” says Catania, who wants to work for an agricultural company in sales and marketing or marketing communications after she graduates in spring 2019.

But first, she’s spending a year abroad. Catania spent the past fall semester studying in London, and now she’s interning and volunteering in Nkokenjeru, Uganda, at a children’s aid organization. There she assists in social work along with supporting the village’s agricultural practices. It’s a dream come true for Catania, who hopes to continue helping improve people’s lives around the world.

Better health for all

When Jordan Gaal graduates from CALS, he’ll be able to add an interesting line to his resume: “Legislative advocacy on Capitol Hill.”

Gaal, a senior double-majoring in life sciences communication and political science, traveled to Washington, D.C., last summer as an intern for the Wisconsin Area Health Education Centers (AHEC). He was part of a state delegation advocating on behalf of the National AHEC Organization, which seeks to enhance access to quality health care around the nation, particularly for rural and underserved populations.

“We visited the offices of Senators Johnson and Baldwin as well as Representatives Grothman, Ribble, Moore, Kind, Pocan and Speaker Ryan to talk about our program, how it benefits Wisconsin and why it should continue to be funded,” says Gaal, whose position as Wisconsin AHEC’s statewide communications assistant continued into the school year.

For Gaal, it’s been the perfect internship to help him make a significant academic transition. When he first came to UW–Madison, he wanted to be a biological sciences researcher, but then he quickly figured out that his true passion lies in communications, advocacy and policy work.

“My general duties are primarily communications and marketing,” says Gaal. “I’ve had the opportunity to create documents for legislators and lawmakers to emphasize the importance of public health issues, such as the need for more health care workers in rural areas. And before heading to D.C., AHEC helped prepare me to make legislative visits.”

The internship, which will last through the end of the academic year, also has Gaal working on news releases, social media, a quarterly newsletter, an annual report, website maintenance and more. The position comes with attentive mentoring and coaching as well as ample independence to pursue assigned projects.

Gaal’s supervisor, Keri Robbins, assistant director of Wisconsin AHEC, takes pride in offering meaningful internship experiences to undergrads. The trip to D.C., she notes, was particularly valuable.

“It will serve Jordan well in future opportunities to engage in advocacy or policy work,” says Robbins. “And AHEC benefited from having the student voice represented in our meetings.”

After graduation, Gaal wants to pursue two advanced degrees—a master’s in public affairs and a master’s in public health—and get experience at a federal government agency. He’s looking for a career very much in line with AHEC’s goals, one that will put him in a position to help improve access to healthcare in rural communities.

“It’s a cause I believe in,” says Gaal.

 

The Science Farm

ON A STILL AND WARM SUMMER MORNING, as scientists drive along the dirt roads that crisscross the Arlington Agricultural Research Station, the fields sweep in a green carpet to the horizon.

This land some 20 miles north of Madison was once part of the vast Empire Prairie, a sea of grassland that stretched south to the Illinois border. So high and thick were those grasslands, history tells us, that they could swallow a rider on horseback.

Named by settlers from New York in the 1830s for their home state, the prairie and its rich soils would prove to be ideal for growing corn and other row crops that are the mainstays of modernday agriculture. And today, the region is home to hundreds of farms, some of which date back a century or more.

It makes sense, then, that this place with its productive soils and old farms would also be home to a most unusual agricultural endeavor— a 26-year-old research project aimed at bridging the gap between past and future farming practices. It’s called the Wisconsin Integrated Cropping Systems Trial, or WICST for short.

On 60 acres of land at the CALS-based Arlington Agricultural Research Station, university researchers from a number of departments within CALS are doing big science with tractors and combines and manure spreaders. Clad in blue jeans and work boots instead of lab coats, these scientists are engaged in ambitious longterm research that is relying upon the study of the ancient soils of the Empire Prairie to point the way toward a sustainable agricultural future.

From this effort, started in 1989 by an idealistic and insightful young agronomy professor named Josh Posner, has come research that shows farmers can both run a sustainable farm and grow enough food to play a significant role in feeding a burgeoning world population. It is important, forwardlooking work at a time when many farmers face an uncertain economic future as well as changing climatic conditions that are only going to heighten the risks associated with bringing a crop to harvest or livestock to market.

“It’s among the most important farm-scale research being done in the UW system,” says Dick Cates PhD’83, associate director of the CALS-based Center for Integrated Agricultural Systems, the administrative home for WICST.

Cates, who also owns and works a managed grazing farm near Spring Green, praises WICST for the quality of its research as well as its unusual long-term approach to studying varied approaches to farming. He uses the research in teaching young farmers in a program he helped found, the Wisconsin School for Beginning Dairy and Livestock Farmers.

The science on sustainable practices particularly resonates with younger farmers, Cates says: “They understand long-term consequences.”

Research at WICST has been conducted on fields that are farmed using three cash grain and three forage-based production systems common in the Midwest. They include 1) conventional corn; 2) no-till corn-soybean rotation; 3) organic corn– soybean–wheat rotation; 4) conventional dairy forage; 5) organic dairy forage; and 6) rotationally grazed pastures. In 1999, Posner added plots devoted to the study of switchgrass and diverse prairie, which has allowed for grazing and bioenergy studies nested within the bigger experiment.

Toiling in their plots at Arlington, WICST researchers (including a steady stream of graduate students) have compiled an impressive archive of publications showing that sustainable farming practices, such as managed grazing and crop rotation, make sense from both economic and ecological perspectives.

They’ve studied everything from the effect of alternative crop rotations on farm profitability to soil health and carbon sequestration. They’ve tallied earthworms and ground beetles. They’ve analyzed weed populations. They’ve learned more about manure than you would suspect is possible.

Among their key findings:

• Organic- and pasture-based farming systems have been the most profitable cropping systems at WICST.

• Organic systems produced forage yields that were, on average, 90 percent of conventional grain systems and as high as 99 percent in two-thirds of the study years.

• Over a 20-year period, all five grain and forage cropping systems— except for grazed pasture—lost significant soil carbon to the atmosphere.

It’s a record that would have impressed and pleased the late Posner, who died in 2012. It is rare for any conversation about WICST not to lead eventually to Posner and his pioneering idea of a decades-long research project dedicated to the science of agricultural sustainability.

Posner, who held a Ph.D. in agronomy and a minor in agricultural economics from Cornell University, had conducted significant sustainability research from South America to West Africa before coming to the University of Wisconsin–Madison. His interest in agriculture grew from his work as a Peace Corps volunteer in Cote d’Ivoire, Africa, in a school gardening program.

Posner was hired by UW in 1985 to coordinate a UW research program in Banjul, The Gambia. He arrived in Madison in 1987 and began teaching and research in the Department of Agronomy. In 1993, he and his family moved to Bolivia, where he led a UW research program on sustainable agriculture for several years. From 1998 to 2001, he directed CONDESAN, an international agency based in Lima, Peru, to support sustainable mountain agriculture across the six Andean countries in South America.

Posner’s widow, Jill Posner, who still lives in Madison, recalled that her husband first started thinking about the project that would become WICST while working in West Africa with farmers who grew crops without the benefit of modern-day fertilizers and pesticides.

“There was a real link between what he was doing in Africa and the low-input systems he wanted to study here,” Jill Posner says. “It was one of those things that he always kept on the back burner. No matter where we were, he was always thinking about that connection.”

In 1988, Posner, a focused and persuasive scientist, would pull together the team that created WICST. His plan was to establish a research project that would compare sustainable land management practices, organic agriculture and traditional approaches. And the project would be ambitious in both size and duration. Research would be conducted on a scale that approximated the conditions on an actual farm. The science would stretch over not just a year or two but decades. Wherever Posner’s work took him around the world, he continued to oversee WICST, reviewing the plans and results and returning to Madison to connect with his research team at least twice a year.

That Posner would propose such an audacious project didn’t surprise those who knew him. He thought big, recalls Dwight Mueller, director of all UW Agricultural Research Stations— and Posner saw something else that many others didn’t fully understand at the time: The eventual emergence of organic and other conservation-minded farming as powerful and necessary trends.

“If you knew Josh, you might have had an inkling,” says Mueller regarding Posner’s long-range vision of field research that would meet the challenges posed by increasingly stressed resources. This was a time, Mueller notes, when crop farming largely meant planting year after year of corn with little rest for the soil. And organic agriculture was thought of by many as a hobby or possibly a passing fad.

“‘Organic’ was a dirty word when we started,” says Mueller.

Randy Jackson, a CALS agronomy professor and grassland ecologist who now leads WICST research and has been involved in the project since 2003, says the crop experiments played an important role in bringing science to bear on organic and other sustainable practices. For such practices to become more widely accepted, it was important to demonstrate that these grain and forage production systems could yield as much as conventionally managed systems in most years, he says.

The two main questions posed by Posner are still in play at WICST, says Gregg Sanford, a research scientist in the Department of Agronomy who has worked on WICST since joining Posner’s lab as a graduate student in 2004: Whether organic agriculture would be able to provide enough calories to feed the world and whether agroecology, or sustainable farming, would be embraced as economically feasible.

Key to the project was its scale, its focus on the long horizon and its collaborative nature, Sanford explains while driving along the project’s dirt lanes.

Conducting the research on the scale of an actual farm-sized operation in large plots has proven a boon, Sanford says, because it lends more validity to the science. Farmers tend to take the results more seriously when they know that the research had to be conducted in the face of the same challenges they face—everything from bad weather to insect infestations to equipment breakdowns.

This element of the research project becomes immediately clear on a visit to Arlington. There is little doubt that this is a working farm with its crops, grazing livestock, and sheds and barns, where begrimed farmhands coax tractors and cultivators and other equipment into working order.

The true-to-life nature of the research is strikingly apparent in annual reports that are similar to the notes kept by scientists in their laboratory notebooks but refer instead to the vagaries of storm and drought and insect scourges.

In a report from 2011, for example, Posner and researcher Janet Hedtcke reported “unseasonable cold well into May resulting in delayed start to the cropping season.” We find out that “in late September, strong winds knocked down a lot of corn, especially the organic corn, which was tall, had big ears way up high, and thin stalks,” they wrote, referring to a particular cropping system treatment.

Or there is the 2012 report, in which Hedtcke laments that crops and livestock endured extreme heat and drought. “Springtime,” she noted, “arrived early with temperatures soaring to above 80 for eight days in March.” Then one can hear the relief of a real farmer when she writes that, after a dry June, “an unforgettable and precious soaking rain came on July 18.”

Such challenges make conducting the research much like farming itself. “We’ve had years where we’re trying to get manure applied and it starts snowing on us,” Sanford says.

“We’ve had years where we’ve had complete crop failures because of the rain.”

But there is a twist, of course. The harvest at Arlington isn’t just of crops but also of science. A lost crop year represents a loss of crops, but it also provides a critical piece of data in a realworld experiment that shows how risky growing particular crops can be.

Even so, the length of the project has allowed researchers to weather the ups and downs. And the many years of data collection have paid off in ways that traditional science, conducted over periods of months or maybe a year or two, has trouble duplicating.

“It has shown the value of a longterm project,” says Mueller. “That can’t be overestimated. There are things you learn only by having a trial for a long time.”

Jackson says such long-term research is crucial when studies involve dynamics that unfold over a period of years or longer. He cites climate impacts as an example.

“It allows us to separate the vagaries of interannual climate variability and actual directional changes,” Jackson says.

Also, natural systems can be slow to respond to change, Jackson notes. Sometimes when a particular treatment is applied to a parcel of farmland, the result does not become apparent for two or three years or more.

Both the size and the length of the project have made the data more realistic, says Sanford, allowing scientists to account better for variables thrown their way by weather and other obstacles.

The value of research flowing from WICST has also been enriched by another characteristic built in by Posner with his original plan—the project’s collaborative nature. From the beginning, WICST has involved not just CALS scientists but also farmers, business owners, nonprofits and, notably, UW–Extension educators.

And, as envisioned by Posner, the research on WICST’s 60 acres at Arlington has been conducted across multiple disciplines in CALS, from soil scientists to grassland ecologists to entomologists.

Entomology professor David Hogg, along with his students, has spent long hours on WICST land sifting through the soils looking for links between soil health and insect health.

“It’s a great laboratory for doing this kind of work,” says Hogg. “And it’s unusual.”

Much of the work at the Arlington plots has focused on the soil, the single resource that farmers value more than any other for providing them a living and the world its food.

The science of soil has been approached from many angles by WICST researchers, with a number of surprising and useful results. Among the more eye-opening work has been the study of soil for its ability to store atmospheric carbon to help mitigate the changing climate. This characteristic has thrust agriculture and soil health and management into the climate discussion in a big way, according to Sanford.

The issue has driven much of Sanford’s work with WICST. In fact, the subject of his dissertation was land management and its effect on carbon in soil, where he comments that “the importance of soil in the global carbon budget cannot be overstated.”

Soil, Sanford reports, contains almost twice the combined amount of carbon found in the atmosphere and vegetation globally. Through his work with WICST, Sanford has been able to demonstrate which practices—using cover crops, for example, or increased crop rotation—help keep more carbon in place and out of the atmosphere.

As was Posner’s intent, the science coming out of the WICST fields has found its way into some of the most prestigious scholarly journals—and, importantly, into the hands of farmers. In the best tradition of the Wisconsin Idea, the shared knowledge from the trials has given farmers new tools for improving their yields, boosting the health of their soil, and protecting resources such as water.

Few are more aware of the power of WICST science than UW–Extension county agents, who spend their days in farm fields and barn lots working with farmers and sharing with them the latest knowledge gleaned from university research plots.

“Arlington research has helped greatly with crop production questions,” says Ted Bay, an agricultural extension agent in Grant County.

Bay cites a heightened interest among farmers in soil and water conservation and sustainable practices as reasons for sharing with them the results of the WICST research. More farmers, he says, are asking how they can use cover crops to protect and improve their soil in row crop production. Research from WICST has confirmed the value of using cover crops to protect soil, and provided information on integrating cover crops in grain production systems.

“Farmers are interested in the longterm impact of production practices that WICST research can help explain,” Bay says.

Gene Schriefer, the agricultural extension agent in Iowa County, in hilly southwest Wisconsin, says he’s had Sanford out to talk with farmers about the WICST research. He says farmers, who are nothing if not practical, tend to be more trusting of information that comes from a research program that has stretched over decades.

“Most research is over two or three years,” says Schriefer. “This research has been going on for nearly 30 years. That’s amazing.”

Schriefer sees particular interest among farmers in research that tells them how to return their soils to health and how to keep it in place in the face of storms that are both stronger and more frequent.

“We’re out here in the hills,” Schriefer says, “and any time it rains, there is not a clear stream out here. That’s our soil.”

Such growing consciousness in the farming community of the connections between agriculture and a healthy environment is heartening to researchers such as Sanford. For Sanford and other WICST researchers, it’s a testament to the power of Josh Posner’s vision all those years ago in distant Africa.

Sanford, tooling around the WICST fields on a summer morning in his beatup pickup truck, stops to show off a fading sign that dates back nearly to the start of the research. He notes the prominent mention of sustainability, agroecology and organic agriculture. Staffers, Sanford says, are reluctant to take the sign down despite its age because it is a poignant reminder of Posner’s hope and optimism.

“When Josh built this experiment, he was setting us up to understand how crop yields and soils respond not only to farm management, but also to a changing climate,” says Jackson. “These are critical questions whose answers should guide agricultural production in the 21st century.”