The Fox, the Coyote­—and We Badgers

Once upon a time during the last few years, a red-haired girl new to the University of Wisconsin–Madison crested Bascom Hill and cast her eyes upon the cozy arrangement of buildings and lawns, the tree-lined city by the fair lake. Her nature and upbringing led her to think: Yes, this is good. I should meet the right boy here. I hope the food is good.

The UW–Madison campus is a well-worn locale for such scouting. Last year 31,676 prospective students scoped out dorms and classrooms. Hundreds of elite athletes measured the environment against their precise needs. Thousands more informal visits were made, all driven by the same question: Can I thrive here?

But our young visitor is in a new class altogether—wild members of the canid clan. As it happens, their food is quite good, and she—technically a vixen, or female fox—did find the right dog. After spending a winter holed up under Van Hise Hall, she gave birth to a litter of eight, and in early March of 2014 began to let the young kits gambol about.

They were a campus sensation—stopping lectures, cars and buses, inspiring a popular Tumblr blog, drawing hundreds of rapt spectators. Their appearance provided a fortuitous teachable moment for David Drake, a professor of forest and wildlife ecology and a UW–Extension wildlife specialist, who was just beginning to delve deeper into studying the foxes and coyotes of Madison.

Coyotes have been intermittent, if secretive, Madisonians for more than a decade. In the last few years reports of coyotes by visitors to Picnic Point have been rising, and people from the Lakeshore Nature Preserve asked Drake if he could investigate. But the rise of the urban fox population is a relatively new canine twist.

“It’s very timely,” says Dan Hirchert, urban wildlife specialist with the Wisconsin Department of Natural Resources. While no comprehensive data have been collected, from where he sits foxes and coyotes are gaining throughout the state. And while the coyotes have been present for a couple of decades, the fortunes of the fox seem to be following the rise in urban chicken rearing.

Because most wildlife research happens in rural areas, we may not know as much as we think about our new neighbors. “Does what we’ve learned about these animals in the wild apply in urbanized settings?” asks Drake. Most major cities employ a forester, but very few cities have a wildlife biologist on staff. Much more common is the pest management paradigm: animal control.

“It doesn’t make any sense to me,” Drake says. “If 85 percent of Americans live in cities, why aren’t we doing more? That’s where people are interacting with wildlife.”

These questions prompted Drake to found the UW Urban Canid Project, a hyperlocal study with far-reaching implications.

“The number of urban canid sightings on campus, primarily red fox and coyote, have been on the rise and have been met with mixed emotions from all different members of society,” notes Drake. “This research aims to understand more about the complex interactions between coyotes, foxes and humans in this urban area—as well as provide information and resources for residents to reduce the potential for conflict with these amazing creatures.”

As morning light seeped into a cold January dawn, David Drake and his grad student Marcus Mueller prepared to lead a small convoy from Russell Labs, winding toward the wild corners of campus to check 18 restraint traps that had been set the evening before.
“Are you feeling lucky today?” Drake asks, climbing into the truck.

“Always,” says Mueller.

“I had a hard time getting to sleep last night,” says Drake. “This is like the anticipation of Christmas morning. Every day you go out to see if you caught something.”

First stop is the old Barley and Malt Laboratory, between the retaining wall of University Avenue and the physical plant. It hardly seemed like habitat, but Mueller traced a clear track laid down by the repeated passage of many small feet. The animals were using the buildings for cover, in transit to someplace else.

Drake is hopeful—he’d already received a call from someone who’d seen a fox at 5:20 a.m. on the football practice field. “They were running through Breese Terrace all last year,” he says. At least one fox was digging in an area under the west side bleachers of Camp Randall for a possible den, notes Drake, but no kits were ever seen there. “It is funny to find these spaces on campus that the animals are using,” says Drake. “I ride my bike by here every day and never really thought about it.”

And in one of the three traps an annoyed raccoon waits impatiently. Donning protective gloves, Drake and Mueller release the coon, who scuttles away, anxious for cover.

Next stop is a small cattail marsh next to Willow Beach, behind the new Dejope Residence Hall. The day before, Drake and Mueller had baited the marsh with parts of a deer carcass. On the short trail we flush an eagle from its perch, perhaps planning its own morning snack of carrion.

This little ecological pocket typifies the habitat opportunities that fox and coyote are exploiting. It’s not big enough to call home, or even to get a regular meal. But link it together with dozens of other nooks and crannies and dumpsters around campus, and the sum total is a complex and productive niche.

Fox and coyote are urban adapters: flexible enough to range across a variety of landscapes, from rural to urban. For animals to survive in a city, they typically need to be this kind of habitat generalist, able to exploit a range of hunting and scavenging environments.

The other part of the equation is habituation—how animals get accustomed to human activities. As a species moves into the city, those who survive realize over time that bad things don’t necessarily happen when they encounter humans. Instead of running at the first sign of people, they sit and watch. This knowledge gets passed down from mother to pup, eventually leading to the Van Hise foxes romping in full view of adoring crowds.

The restraints behind Dejope are set for fox, and this morning there is nothing. Drake looks around and connects the dots in the surrounding environment. West across the ice is University Bay Marsh, where four more restraints await. A few ticks to the north is Picnic Point, and the lake beyond.

The last traps of the day are located in the Biocore Prairie, where the research began when a few trail cams confirmed that a group of coyotes were ranging through the preserve, and probably enjoying the fruits of the Eagle Heights gardens as well.
Drake hopes to learn how urban agriculture is influencing canid behavior. Backyard vegetable gardening is flourishing, and each year more city dwellers add chicken coops to their homesteads.

The chickens are an obvious attraction—chickens have probably been preferred canid targets since even before their domestication. Gardens also attract the small mammals that canids prefer. They will even snack on berries and vegetables.

Last year Drake secured four radio collars—two for each species—and, with the assistance of Lodi trapper Mike Schmelling, researchers were able to collar a pair of coyotes and one fox. Among the first discoveries was that the animals are running the frozen lake. The researchers learned this when one collared coyote disappeared. At first they suspected a malfunction, but a citizen report led them to Maple Bluff, where they reestablished radio contact. The coyote had apparently run all the way across the lake, possibly snacking on ice-fishing gut piles along the way. Another ran north and was killed by a car on County M, near Governor Nelson Park.

This year the research hits full speed, with 30 fox collars and 30 coyote collars available. The ambitious work plan includes collaring an entire fox family, kits and all.

And in the snow-covered landscape of the Biocore Prairie, the first glimpse of the third restraint trap offers a rush of hope. The area around the restraint is beaten up, with dark leaves interrupting the white. An animal was clearly held at some point, but all that’s left is a bit of hair and a kinked and ruined cable.

Back in the truck, Drake teases Mueller. “Marcus, I don’t have a good feeling about your luck.”

“Not yet, anyway.”

“You’re not an unlucky person, are you?”

“I hope not.”

“Because I have fired more than one graduate student for being unlucky . . .”

It’s just as dark and even colder the next morning, yet the party adds an undergraduate wildlife ecology student, Cody Lane, and Laura Wyatt MS’87, a program manager with the Lakeshore Nature Preserve. John Olson, a furbearer biologist for the DNR, is in town, and has come to check out the project before putting in a day of lab work.

Behind the Barley and Malt Laboratory, Olson kneels down to evaluate the tradecraft of the empty restraint—a simple loop of airline cable noose suspended from a dark length of stiff wire. “They don’t even see these as traps. They see them as sticks,” Olson explains.

These unique cable restraint traps were named and developed with DNR assistance as part of a national humane trap research program in the early 2000s. “The important thing with these kinds of sets is non-entanglement,” he says. The radius of the multistrand wire must be clear of any potential snags. The size of the loop is determined by the animal you’re selecting, while a stopper keeps it from getting too tight. It works much like a choker collar.

During testing they trapped just over 200 coyotes, and only two died. One had a bad case of mange and died of exposure. The other was shot by someone who didn’t realize the animal was restrained. “It’s a very safe tool,” Olson says. “Cable restraints never damaged any coyotes in the three years that we studied them.”

The convoy moved on to Willow Beach—and, finally, success. A young male fox waits suspiciously, huddled in the reeds. The wind probes at his deep winter coat while the party retreats and summons Michael Maroney BS’85, a veterinarian with the UW–Madison Research Animal Resources Center.

Together Mueller and Maroney estimate the fox’s weight at 12 pounds, and draw a mix of ketamine and xylazine. Mueller secures the animal with a catch pole while Maroney injects the cocktail into the rear leg muscle, provoking an accusing glare from the fox. The clock starts. Within six minutes Maroney looks at Mueller and announces: “He’s clearly gorked.”

Everybody laughs at the non-technical yet thoroughly accurate terminology, and the work begins. They figure they have about 40 minutes. Laying the animal out on a white towel atop a blue tarp, Mueller secures a cordura muzzle, then pulls out electric clippers and shaves one dark foreleg to make it easier to find a vein. Maroney watches his technique while the undergraduate Lane records data.
The fox breathes steadily, and the three talk quietly, as if he were only asleep. Without the wind ruffling his coat, the fox seems smaller, more vulnerable. After the blood draw, nasal and fecal swabs are taken, and the mouth examined. Finally, they weigh the animal—a sturdy 13.5 pounds—and affix the radio collar.

Removing the muzzle, they carry him away from an opening in the marsh ice—a gorked animal doesn’t always behave rationally—and lay him out again on the tarp, out of the wind. A few minutes later and a dark ear twitches, as if to displace a fly. A few more minutes, and the ear twitches pick up. Suddenly the fox stands up shakily, and surveys the audience of onlookers. He quickly takes cover in the marsh, where he gathers his wits for a few more minutes, then slips from view.

Mueller and Drake are giddy, ebullient. “We are off and running,” says Drake. “That was pretty cool.” Last year it took forever to catch a fox; this year they begin with one. “Great start,” says Mueller, and then recounts the steps to himself in a low voice, as if to help remember: the sedation, the blood draws, the recovery.

Mary Rice first saw the coyote in her backyard sometime in the summer of 2012. It was getting dark, and first she wondered, “Whose dog is that?”, followed quickly by: “Oh, my god, a coyote.”

“We were a little alarmed,” she says.

Rice canvassed the neighbors, warning them there was “a coyote lurking” about. Some didn’t know, others did, and some even thought they’d seen wolves. She was wondering how to deal with it, who to call, when she saw another one, smaller. “Remove one, there will be another,” she realized.

A graduate coordinator in the Department of Food Science, Rice remained somewhat unsettled for a few months, worrying about her cats and unsure about her own safety. Then one day at work she learned about Drake’s UW Urban Canid Project and decided to give them a call.

“Can you try to track it and figure out what it’s doing here?” she asked. “We can hopefully live with it. If we’re not going to be able to remove it, maybe we can learn from it and learn how to live among them.”

Before long, with the cooperation of another neighbor, a restraint trap was set. This was Mueller’s first solo set: he decided where to put it, and configured and camouflaged it. Within a week, in early March they had a 36-pound male coyote who had been cutting behind a brush pile. On her way to work, Rice stopped to see the animal and help the team record its vitals. She couldn’t wait to tell her coworkers why she was late.

Rice’s coyote experience is a perfect example of how the project can work, says Drake, with outreach engaging members of the public and connecting them with scientists in the field. On most trap-checking mornings Drake’s team has company—each day a new handful of visitors. Sometimes they’re wildlife students or other friends of the program, but often they’re just curious early risers who follow the group’s progress on social media.

And with hundreds of followers on Facebook and Twitter, public fascination is strong. Because of our strong cultural connection to dogs, our affinity may even be a little hardwired. From Wile E. Coyote and fox or coyote tricksters in folklore to the Fantastic Mr. Fox, these are animals we all know on some level, however mythic.

Still, fox and coyote don’t get quite the same reception. The fox is easy to anthropomorphize. It’s small, cute and generally non-threatening. Coyotes aren’t typically seen as often, and your first thought can be, like that of Mary Rice: Whoa, that’s a pretty big animal.

“Just because you see a coyote doesn’t mean it’s a bad animal, and doesn’t mean it’s going to create problems for you or that you should be afraid of it,” says Drake. The key is to not create, or exaggerate, a conflict. And that’s almost always about food. It’s important to secure bird feeders and outside pet food, and to take care with pets out of doors. If the coyotes become too bold, make an effort to scare the animals away. “We’re really trying to help people to understand how wonderful it is to have these animals here, but also to be vigilant,” Drake says.

“Are you nocturnal yet?” I ask Mueller as I climb into a white UW van at 9 p.m. in early March. He laughs—it won’t be long now. As soon as early-morning trap checks are done, he’ll be swinging full-time on the second shift. These dogs are nocturnal, and if you want to learn where they are at night, you’ve got to get out there with the radio tracker.

The research plan calls for tracking each animal at least once a week. Some nights it’s boring, and Mueller catches naps between hourly triangulations. But the newly collared fox has been a real challenge. He was tracked one night moving from south of Fish Hatchery Road and Park Street all the way up to John Nolen Drive, where he spent time on frozen Monona Bay and eventually made it to Muir Woods on campus. That’s about four miles as the crow flies—never mind the urban labyrinth he had to navigate between those points. He did all that traveling within a five-hour period.

“It truly was a game of cat and mouse trying to keep up with him that night,” says Mueller. Is he a young transient who hasn’t yet established a home range? Is he trying to find a mate? Or can home ranges for urban foxes really be that big?

Some nights Mueller can track only one animal, but on others they are close to each other. On one recent night the fox and the coyotes were all on campus, just a short distance from each other. “I was flying all over campus,” says Mueller. “It was a crazy night of telemetry.”

It was a perfect scenario for answering a really big question. In wilder terrain foxes and coyotes are mutually exclusive, but Madison is different. “We know from the animals we’ve got on radio that the fox and the coyote are sharing the same space, and sometimes they are sharing the same space at the same time,” says Drake. “They are crossing paths.”

Are the foxes using humans and elements of our built environment to protect themselves from coyotes? Or are there simply enough resources that they don’t have to compete as strictly—more rabbits and squirrels, more compost piles and chicken coops?
The scientists are a long way from answering those questions. First they need to relocate the coyote.

Mueller parks around the corner from Mary Rice’s house in a residential pocket south of the Beltline and raises the antenna, a three-element Yagi that looks like a refugee from the old days of analog TV.

The first reading comes from the west, and from the strength of it Mueller guesses we’re a mile or more away. Crossing back over the Beltline, a little under a mile as the crow flies, and another reading: now the signal’s coming from the east. Another three-
quarters of a mile into a dead-end parking lot, and the signal is now east and south. But back over the Beltline.

In quarter-mile and half-mile increments Mueller is in and out of the van, swinging the antenna around, squawk box to his ear, taking compass readings. After a few more readings he finalizes the coyote’s location in a small wetland not far from one of the many bike paths that probe south from the city. He stayed put until 2 a.m., when Mueller called it a night.

“I can’t wait,” says Mueller, thinking ahead 12 months, when he’s got hundreds of hours of data plotted on a map and can begin to see patterns. “The underlying goal of this project is to be able to coexist with these animals more effectively, to avoid conflicts,” he says. “We don’t want to have to remove coyotes from a population because they are too habituated to people.”

As a summer job during college, Mueller used to take calls at a wildlife rehab center in Milwaukee. “A lot of times people just don’t know much about the ecology and life history of these animals, and that lack of understanding leads to fear,” he says. One call in particular stuck with him, a man worried about a turkey walking around in Milwaukee.

“He said, ‘You’ve got to take it back to nature. It’s not supposed to be here,’” Mueller remembers. But the turkey had already redefined nature—and so have coyotes and foxes and deer and raccoons and . . .

“Cities aren’t going anywhere,” says Mueller. “And the way that these animals are adapting, I think it’s only going to allow for more animals to continue this trend.”

Keep up on all the latest information from the UW Urban Canid Project on Facebook and on Twitter: @UWCanidProject. If you have any questions, or are interested in observing or volunteering, please email: uwurbancanidproject@gmail.com.
To see more campus fox photos by E. Arti Wulandari, visit: http://go.wisc.edu/campusfoxes.

Unpuzzling Diabetes

The body makes it seem so simple.

You take a bite of supper, and the black-box machinery of metabolism hums into life, transforming food into fuel and building materials. It’s the most primal biology: Every living thing must find energy, and must regulate its consumption.

But for an alarming and ever-increasing number of people, the machinery breaks down. The diagnosis? Diabetes.

Alan Attie, a CALS professor of biochemistry, has been peering into the black box for two decades now, trying to identify the pathways in our bodies by which the disease is formed. “You can’t find a better excuse to study metabolic processes than diabetes,” he says. “It’s very, very rich.”

Type 2 diabetes, caused by an inability to produce enough insulin to keep the body’s blood glucose at normal levels, is a global health crisis that has accelerated at a frightening speed over the last 20 years—roughly the same time Attie has been studying it.

It’s an enormously complex disease driven by both genetics and the environment. A DNA glitch here, an external variable there, and the body slides irretrievably out of balance. But only sometimes. Most people who develop type 2 diabetes are obese, yet most people who are obese don’t actually wind up diabetic.

Tracking this riddle has led Attie and his lab to several major discoveries, chief among them identifying two genes associated with diabetes: Sorcs1 and Tomosyn-2. Through years of elaborate experimentation, Attie and his team teased them from the genetic haystack and then relentlessly deciphered their role in metabolic malfunction.

Science has uncovered more than 140 genes that play a role in diabetes, yet genetic screening still has little value for patients. As with any part of a large and complicated puzzle, it’s hard to see precisely how Sorcs1 and Tomosyn-2 fit in until we have more pieces. The biology of diabetes is so complex that we can’t be certain what the discoveries may ultimately mean. But both genes have shed light on critical stages in metabolism and offer intriguing targets for potential drugs.

Attie need not look far to replenish his motivation. His own mother suffers from diabetes, and she used to quiz him weekly about when he would cure her. “The painful answer is that translation of basic research into cures takes a long time,” Attie once told the American Diabetes Association. “The most important clues that can lead to cures do not necessarily come from targeted research or research initially thought to be relevant to the disease.”

Alan Attie grew up an expatriate in Venezuela, where his father, Solomon, originally from Brooklyn, New York, ran a textile factory (Attie’s mother had family in South America). Poverty and then World War II had kept Solomon from traditional schooling, but he managed to put himself through high school at night, and he nurtured a deep passion for literature, poetry, history and politics. At home he ran the family dinner table like a college seminar. “Our evening meal was like a 20-year course,” recalls Attie. “It was the most stimulating part of our day growing up. I was reading Shakespeare with my father and my siblings when I was 10 years old.”

Still, Attie wasn’t quite prepared for the academic rigor of UW–Madison when he arrived in 1972. He’d never had to work particularly hard in high school and was shocked by how much time and effort college required. His grades were poor and his introduction to chemistry lackluster.

But the BioCore curriculum—an intercollege program focusing on doing science, not memorizing facts—turned Attie’s natural inquisitiveness and enthusiasm toward science. During a cell biology course where his lab reports had to be written like journal articles, Attie decided he really wanted to be a biologist. Following graduate school at the University of California, San Diego, he found himself back at UW– Madison as a young assistant professor. Ten years had passed since his freshman matriculation.

Attie’s first research focus was cholesterol metabolism, but his curiosity led him elsewhere. Until 2001 he held a joint appointment with the School of Veterinary Medicine, where he taught an introductory class in biochemistry. While preparing for the class he read broadly in metabolism and found himself continually drawn toward the quandary of diabetes.

Increasingly he found himself suffering from “discovery envy,” he says. “And then I finally decided one day I do want it to be me.” Midcareer course changes are never easy, but Attie plotted a careful transition that gained momentum with hard work and good fortune.

In 1992 Dennis McGarry, a prominent diabetes scholar, published a provocative thought experiment in Science. It had been observed for centuries that diabetics had sweet urine, and one of the earliest researchers in the disease, Oskar Minkowski, had surmised that diabetes was therefore a dysfunction of sugar metabolism. McGarry speculated that if Minkowski had had no sense of taste and had relied instead on the smell of a diabetic’s urine, he would have smelled ketone bodies, a hallmark of lipid metabolism. Might he have concluded instead that diabetes was a defect in lipid metabolism?

Soon afterward, McGarry and Attie wound up at the same research symposium in Edmonton and shared breakfast every morning. “I’m really interested in diabetes,” said Attie. “Is there room for someone like me who has been working on lipid metabolism for 20 years?” McGarry encouraged Attie, a pep talk that gave him confidence that maybe he wasn’t committing career suicide.

Gradually Attie’s new focus gathered steam. When another UW diabetes researcher left for Washington state, Attie was able to bring on researcher Mary Rabaglia from that lab. She was highly skilled in the lab manipulation of pancreatic islets, the home of the beta cells that produce insulin. Her arrival jump-started Attie’s efforts. “It was an unbelievable stroke of luck because she brought all that expertise,” says Attie.

Attie also felt he needed a new analytical toolbox, and he saw real potential in using mouse genetics to study diabetes. With one small problem: He didn’t know any genetics. So he went to the Jackson Laboratory in Bar Harbor, Maine—a global center of mouse research—and took a mouse genetics course (which he now teaches there).

The learning soon paid off. Gene chip technology was just becoming available, and industry pioneer Affymetrix was looking to commercialize the expensive technology. The company was interested in funding labs to demonstrate that the power was worth the price. Attie proposed looking at how genes were turned on and off in the fat-storing cells of diabetic mice, and Affymetrix approved the project.

Exploring gene expression—which genes get turned on and off—was an important first clue in figuring out which genes might contribute to diabetes. With thousands of proteins and a still unknown quantity of genes in play, diabetes is vexingly elaborate. Gene chip technology brought previously unimaginable power to the equation. “The reason for doing genetics is we can’t imagine the complexity of these processes,” Attie explains. “We really do need the serendipity of genetics to find our way.”

Attie sent Sam Nadler, a new M.D./ Ph.D. candidate, off to Maryland and California for training. It was an ambitious project, and the old analytical tools broke under the mountain of new data. Enlisting the help of Brian Yandell, a CALS professor of horticulture with a joint appointment in statistics, they were able to interpret their data.

In late 2000 the team published the first paper on genome expression changes in diabetes using gene chip technology. It was premature to get too excited—they were, in effect, translating a book of unknown length, and had only finished the first of many chapters.

But it was an important demonstration of the power of their new tools. And Attie and his lab were now a known quantity in the world of diabetes research, and part of the conversation.

Attie’s team could now assess any DNA they got their hands on, but there was still too much static hiding the working genes. Only by basing his experiments on other, more tangible clues could Attie find anything useful.

He decided to tackle the obesity link. “Most people who have diabetes are obese, but most people who are obese don’t have diabetes,” he notes. To get at the problem, Attie’s team took two strains of lab mice: a standard control strain known as “black 6” (B6) and a diabetic strain (BTBR) that, when the mice became obese, were diabetic. The team intercrossed the two strains for two generations, testing the second generation of mice for diabetes. Offspring were strategically bred to enable the lab to pinpoint the genes responsible for diabetes susceptibility.

The collaboration that had begun with Brian Yandell now expanded to include Christina Kendziorski, a professor of biostatistics with the School of Medicine and Public Health. Teasing conclusions from large data sets was an exciting new field, and the team saw real potential for developing new techniques— and they had the statistics grad students to do it. Some even took up residence in Attie’s lab to be closer to the puzzles cascading from each successive experiment. It was like game after game of Clue, only with a half million possible rooms, a half million possible murder weapons, and a half million possible suspects. And as many homicides as you wanted to look for. Some computations took days.

Ultimately they were looking for genes, but what they found at first were just general target zones, located on chromosomes 16 and 19. That was a big first step, but chromosomes are constructed of many millions of base pairs—the building blocks of DNA . Considered relatively small, chromosome 19 still runs to about 61 million base pairs. The first round of sifting reduced the search zone to a neighborhood with only 7 million base pairs, an almost 90 percent narrowing of the field.

Pinpointing the gene required a constant shuffling of the genetic deck, counting on the random nature of sexual reproduction to winnow away the chaff, revealing the kernel of the gene. It’s a process that can take years, measured in mouse generations. Finally, in 2006, they were able to pinpoint the precise location of Sorcs1. It was a triumph, but it also set the stage for heartbreak.

Meanwhile, other projects kept rolling. Sushant Bhatnagar, a postdoctoral scholar in biochemistry, was working on the other target zone—chromosome 16. In 2011 he zeroed in on Tomosyn. “It was crazy,” he says of the work needed to sift through so many mouse generations.

But in the end they discovered that Tomosyn-2 played a critical role in diabetes. Tomosyn was also more willing to give up its secrets. Most of the myriad proteins in a beta cell are positive regulators, which means they facilitate flipping the insulin switch to “on.” Tomosyn is an off switch—one of very few known to exist.

Though mouse and human diabetes are different, the lab confirmed that the human version of Tomosyn plays a similar role. Now the challenge is using the clue to develop a targeted therapy. “Loss of insulin secretion leads directly to diabetes,” Bhatnagar explains. “If you can fix insulin secretion you can fix the majority of diabetes.”

Finding Sorcs1 had been difficult enough, but unlocking how it worked would prove devilishly complex. Two students tried and failed, and eventually left research altogether, demoralized by the dead ends. Attie felt terrible. “I always feel responsible for everything that goes on in the lab,” he says.

Then, in 2012, Attie welcomed a new postdoctoral scholar. The only problem was that Sorcs1 was a beta cell problem, and Melkam Kebede did not come to Madison to work on beta cells.

A child prodigy from Ethiopia by way of Australia, Kebede was through college by age 18 and had her Ph.D. at 23. After spending most of her career on beta cells, she was looking for something  different in her second postdoctoral position. Able to go almost anywhere, she chose Madison, and Attie.

“Of all the places I interviewed, Alan was the most passionate about teaching,” Kebede says. And she liked the way he encouraged people. She’d always been told that she was exceeding expectations, and nobody challenged her during interviews. Except for Attie. “I wanted someone to push me more, so I can do more than what I’ve been doing,” she says.

Pushing people, of course, is a delicate process, and easily fumbled. Attie instead seems to pull with a magnanimous curiosity. And with Kebede he was patient but persistent. Attie would keep asking: Why were the Sorcs mice diabetic? “You still have the parents of these mice waiting in the hallway at the hospital,” he would say. “They are buying so many coffees. You’ve got to come up with a reason why they are diabetic.”

Finally, Kebede couldn’t resist the puzzle—the opportunity to find the link between obesity and diabetes. While the lab hadn’t cracked Sorcs, they had narrowed the focus. And Angie Oler, an invaluable technician with 20 years of experience, would help her get the end game rolling.

In an obese person, cells do not respond completely to normal insulin levels—this is called insulin resistance. To compensate, the body typically produces more insulin. Type 2 diabetes develops when the insulin resistance outpaces the body’s attempt to make more. Sorcs seemed to play a role, but how?

“There are so many things in the body that contribute to controlling glucose levels in the blood,” Kebede explains. A beta cell has to sense an increase in glucose and secrete insulin, which then triggers other reactions that lead, ultimately, to glucose being removed from the blood and absorbed by the cells that need it. Sorcs1 could work anywhere in this great game of cellular call and response.

Despite all of the genetic and biochemical tools at Kebede’s disposal, it was ultimately a simple observation in a microscope that yielded the key. Insulin is manufactured in advance and stored by beta cells in the pancreas, then released as needed. Typically only 1 to 4 percent of the insulin is released at any one time, and a healthy beta cell would simply reload and release more insulin as needed. Examining hundreds upon thousands of cells, Kebede realized that the diabetic beta cells were partly emptied of insulin—but not enough to reveal an insulin secretory dysfunction.

The problem was that a standard lab testing for insulin production was a one-shot deal. The Sorcs1-deficient cells could handle that first test, but not a second test. Finally she understood: The diabetes was caused not by a lack of insulin, but by a failure to reload in a timely way.

The team had the answer—but after their first submission to the prestigious Journal of Clinical Investigations, they were asked to do 22 more experiments.

Kebede had been thinking along the same lines and had already begun the additional work. “We wanted to make sure we got the story right,” she says.

It took an extra eight months, but in August 2014 the paper was finally released. It was an exciting and novel find. In type 2 diabetes, it often seems as if the insulin-producing pancreatic beta cells are wearing down. The Sorcs1 discovery suggests a possible explanation for that, and also provides an important change in how to work with beta cells.

Around the same time, a related discovery came from, of all things, a single-celled organism called Tetrahymena thermophila being studied at the University of Chicago. Attie and Kebede went down to brainstorm with Aaron Turkewitz, a professor of molecular genetics and cell biology. It was an inside-baseball connection, the kind that might take pages to explain and doesn’t show up in grants or co-authored papers. But it personifies the role of a researcher like Attie in an endeavor as complex as decoding diabetes.

“His interests at the most basic scientific level have immense medical implications, and in that way, he connects to a large swath of investigators,” explains Peter Arvan, M.D., Ph.D., director of the University of Michigan Comprehensive Diabetes Center. “There are few like him, but he is a model investigator for the 21st century. As the science gets more complex, the field needs investigators like Alan to connect us.”

Once upon a time, Alan Attie had a bumper sticker that said, “Don’t believe everything you think.”

And Attie thinks about so many things. He makes very good wine and is an accomplished amateur photographer. As much as he loves research, he’s passionate about teaching. Conversations glide from the unification of Germany and money in politics, to Ebola and science funding, to income inequality and student debt.

Attie’s not the happiest of scientists right now. As the United States has reduced its lead in science funding, he’s become acutely aware that the kind of midcareer leap he made into diabetes would be impossible in today’s funding environment. He’s got fewer mice in inventory than at any time in recent memory—and to him that means discovery is languishing.

“We can’t pursue all of our good ideas. We can’t pursue all of our bad ideas, either. But we don’t know which ideas are good or bad until we try. The thing is, we’re not trying as much,” he concludes, frustrated. He worries that we’re losing our edge.

For example, he has a lead on a protein that appears to be involved in both Alzheimer’s and diabetes—perhaps the two greatest challenges to health care financing. “I won’t write the grant because it has zero chance of receiving funding,” Attie says. I

In an age where science seems so often a political pawn, it’s refreshing to hear it talked about as a human ideal.

In Attie’s vision, scientific thinking isn’t just running the numbers and picking the ones you like. It’s about “being self-critical, being introspective about how you think and what algorithm you’re using to arrive at a conclusion about anything in the world,” says Attie. “If that were a widespread value, I think our society would be different, better. We would have less hatred, less racism. We would be more nuanced in the way we judge other people.”

Meanwhile, there are mice to study and students to train. Attie’s been involved in the Collaborative Cross, a massive multi-institutional effort to refine mouse genetics to better allow the study of human disease. Using new mice strains, his team is beginning a major fishing expedition, a multiyear project focusing on insulin secretion and beta cell biology in general—utilizing brand new genetic techniques that already are being hailed as game-changing.

Attie knows there will likely be moments of eureka as well as dead-end heartbreak. The team that he loves so much will grow and change as members adapt to the shifting landscape of discovery. He’ll miss the old students and technicians as they move on, but he’ll gain new students and collaborators as he keeps asking the questions that come so naturally to him.

“Being in science is very humbling because I’ve been wrong about a lot of things over time,” says Attie. “That’s part of learning to be a scientist—and yet I think it’s also part of learning to become a better human being.”

Microbes & Human Health

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

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

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

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

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

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

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

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

Coping with the Climate

It’s late May, weeks before southern Wisconsin would be locked into a scorching drought, and Kirk Leach BS’78 is worrying about the weather. The grass around his house is already brittle and yellow. A hose snakes across the driveway, trickling moisture over some sad and thirsty new aspens.

But it’s the corn planted just on the other side of his kitchen garden that troubles him. There are patches—hand-high daggers of green—but there is not enough height, not enough uniformity and just plain not enough of it coming up. “This is the last corn I planted, two weeks ago tomorrow,“ he says. “You’d expect a little more growth than that.” He squats above an empty row, probing through three inches of crumbling earth until he unearths a seed, hard and polished as if just spilled from the bag.

Every farmer has an opinion about the weather. Leach remembers when he was young and everything germinated, even seed just thrown on the ground. But in Leach’s mind it’s these little mini droughts—two or three weeks in a row without rain—that have his attention. “Whether that’s significant enough or evidence of climate change I don’t know,” he muses. “Is it because I was a young, carefree 20-year-old like my sons that I didn’t think about it? Whereas now all the responsibility is mine, and so I’m worrying about every time the next rain is going to come?”

That’s the kind of conundrum that climate change presents to Wisconsin farmers as they’re forced to adapt to wild swings in the weather. Some trust the science, but many have questions, too. They’re all practical scientists with their own, very personal sets of data and research concerns.

The reality is that they’re already adapting to climate change, just as they’ve adjusted to so many other challenges. They’re planting earlier. Schedules for vegetable canneries and cranberry harvest have shifted later to reflect consistently warmer autumns. Even the USDA plant hardiness zone map was updated this year, showing Wisconsin a half-zone warmer than in 1990.

But the forecast calls for a whole lot more, in the way of both opportunity and challenges. The simplest take is that slowly warming temperatures may help boost agricultural production by extending the growing season. But higher temperatures could also reduce corn and soy yields and lead to more pest problems. Higher annual rainfall and more intense storms could mean more soil erosion.

Those broad-brush projections are statistical abstractions for any given farmer. Wherever the weather compass spins, the challenge is to craft a livelihood from sunshine, dirt and water.

The silver lining: a generation of stress in the farm economy has left a population of survivors, farmers who are hungry for information and who are lean and agile enough to act on it. If you have the skill and luck to bring a harvest to market, prices have been good. But with input costs soaring ever higher, extreme climate events can make farming seem more like placing a bet than following a business plan.

The growing season in Wisconsin has lengthened by two to three weeks over the last half-century—a big change over a short time. But because spring can be cold and late one year and early the next, some people tend to chalk it up to variability.

Agronomy professor Chris Kucharik BS’92, PhD’97 has no doubt that it’s climate change. Simply put, the earth is like a giant car, and increasing the amount of carbon dioxide is like rolling up the car windows on a sunny day. But under the hood is a series of massive mathematical models that attempt to mimic and forecast such fundamental earth forces as wind, temperature, evaporation and photosynthesis.

Early in his career Kucharik spent a few years in the far northern boreal forests of Canada helping to fine-tune these climate models. When he grew dissatisfied with the abstraction, he decided to try something closer to home: fit agriculture into the models. Honing in on local, Midwestern problems, he became one of the state’s foremost experts on climate and agriculture, with a joint appointment in the CALS agronomy department and the Nelson Institute for Environmental Studies.

Kucharik knows better than most how dense the science can get, but he is adamant that evidence for climate change is clear and overwhelming. In fact, he can even show how it’s helped agricultural productivity in some locations in Wisconsin over the last few decades. It’s not easy to tease out, because crop genetics and management practices have significantly improved over the same period. But trends in precipitation and temperature during the growing season from 1976 to 2006 explain more than a third of the variability in corn and soybean yield trends, he says.

The bad news is that this productivity trend might be hurt by continued warming without adaptive measures. Indeed, for each additional Celsius degree of future warming, corn and soybean yields could potentially decrease. With luck, modest increases in summer precipitation could offset this. Unless, of course, it fails to rain at all.

Growing Future Farmers

REBECCA CLAYPOOL MS’09 is not color-blind. She knows her house is orange and that the steel shed is blue. Her hands planted the fulsome rows of lettuce and kale and chard—now lush, late-season waves in eight shades of green. She marvels at the funky purple berries in her hedgerow.

But that red barn? “I always wanted a yellow barn,” she explains. But painting is low on the chore list at the Yellow Barn Farm, established in 2010. Claypool’s just finished her second growing season and her mind is already on next year—how much to plant, procuring more compost, relocating a greenhouse. “Some day I will paint it yellow,” she vows.

Born and raised East Coast and urban—in West Philly, to be precise—Claypool is two generations removed from farming. The daughter of a school nurse and an architect, she attended Quaker school and a small liberal arts college in Maine. But on a high school exchange program she caught the farming bug. “I harvested my first potatoes, milked my first cows, gathered my first eggs,” she remembers. “I was looking for something, and it just clicked.”

After college Claypool learned cheese-making and worked on established organic vegetable farms in Pennsylvania and Minnesota. She remembers driving through the Midwestern farmscape for the first time and the revelation of that rich, dark soil unfolding to the horizon. Eventually she wound up studying agroecology at CALS, where she still works as a researcher on the Veggie Compass, a tool that helps farmers determine production costs. A year after finishing her master’s degree she took on 10 acres in Avoca, west of Spring Green.

Claypool’s young operation is pocket change in Wisconsin’s $60 billion ag economy, but it poses a pressing question: Who are our future farmers? Only about 2 percent of Americans now live on farms, and only half of them actually farm. Rural populations continue to age and decline. Farm kids used to be the logical next generation, but that’s now a very small pool of potential applicants to cultivate the farm belt. And agriculture has become so capital intensive that if a farm kid wants to farm, generational transfer is tricky.

Politicians always tout the hiring of more police officers or teachers, but during Farm Bill hearings in 2010, U.S. Secretary of Agriculture Tom Vilsack abandoned his prepared remarks to extemporize on how the country needs 100,000 new farmers. “I think it’s important that we focus an aggressive effort on helping beginning farmers begin,” he argued.

On the state level, Paul Dietmann concurs. “We need people to work the land,” says Dietmann, until recently the director of the Wisconsin Farm Center at the Department of Agriculture, Trade and Consumer Protection (DATCP). “The average age of a farmer in Wisconsin is 55 and keeps getting older and older. At some point we’re not going to have enough people to take over that working land.”

Farm kids are still important players in the future of agriculture, but there’s also a new breed of grower heading for the land. The USDA reports that about one-fifth of all U.S. farms are operated by a beginning farmer, defined as someone who’s been in the business less than 10 years. Demographically speaking, these new farmers—when compared to established agriculturalists—are more likely to be female, non-white or Hispanic. And while they generally are younger, in 2007 nearly a third were 55 or older.

What can be done to support and encourage those who see the opportunity and accept the myriad challenges of farming? People and programs across CALS are trying to answer the call.

In January of 1886, 20 young men gathered on the wintry Madison campus for an innovative 12-week indoctrination in agricultural arts at CALS. They sat through 60 lectures on everything from road building to manure; more than a third of them focused on veterinary concerns. One hundred and twenty-six years and several agricultural revolutions later, the Farm and Industry Short Course is now the longest-running agricultural curriculum in the state.

Its intensive certificate program remains a crash course in essential farm skills, with more than 50 courses ranging from dairy cattle reproduction and business management to pest control and welding. Coursework runs for 15 weeks outside the growing season and helps beginning farmers launch into a challenging, changing business environment. But that’s not the only farmer training on campus. In 1989 CALS opened the Center for Integrated Agricultural Systems (CIAS) as a research center for sustainable agriculture. It offers an array of workshops, most of them two or three days, for beginning dairy and market farmers.