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.