Of Pests and Pathogens

Imagine you’re standing in a sun-drenched field full of lettuce plants. There’s a gentle breeze and a smattering of tiny insects flitting about. It’s a pleasant scene, right?

Now let’s say one corner of the plot is contami- nated with the deadly human food-borne pathogen Salmonella enterica, due to dirty irrigation water.

Could the insects, which hop from leaf to leaf feeding on plant sugars, play a role in spreading the contamination further afield?

“As insects feed and wander around on contami- nated plant surfaces, it’s possible that they pick up Salmonella, so we decided to ask if they are playing a role in food safety,” says Jeri Barak, a CALS professor of plant pathology.

It’s an important question. Salmonellosis is one of the leading causes of acute bacterial gastroenteritis in the United States, responsible for an estimated 1.4 million illnesses, 15,000 hospitalizations and 400 deaths annually. In recent years, there have been more salmonellosis illnesses linked to fresh produce than to animal products. Yet very little is understood about produce-associated outbreaks, including basic information about how human pathogens survive and spread on plants.

To test whether plant-eating insects play a role, Barak teamed up with CALS entomology professor Russell Groves to design experiments assessing the ability of two common crop insect pests—the aster leafhopper and the green peach aphid—to pick up and spread Salmonella.

“Because we work with human pathogens in my lab, we never get to do research outside, so it was important to have someone like Russ Groves on board,” notes Barak. “He’s a UW–Extension ento- mologist, so he has a lot of experience in the field, and he pushed us to be as practical as possible.”

In one set of experiments, insects were given a piece of Salmonella-contaminated leaf material to munch on for 24 hours. In another, they spent the day drinking Salmonella-laced sugar water through a protective barrier that prevented physical contact between Salmonella and

insect. In both setups, the insects were then transferred into a series of clean environ- ments over the next 48 hours to see if—and how long—the contamination lasted.

In both cases, the insects readily picked up Salmonella, and once contaminated, most stayed contaminated.

Those that ate tainted leaves became contaminated inside and out, harboring Salmonella in their guts as well as on their feet and antennae, and when they were trans- ferred to clean tubes, they spread the bacteria to fresh leaf material.

For insects that drank the Salmonella- laced sugar water, the bacteria got into their guts—and also found a way out.

“They excreted the Salmonella through honeydew—that’s a nice word for insect poop. Even after 48 hours, they were still pooping it out,” says Barak.

Honeydew, they also found, serves as a nutrient-rich fertilizer that helps Salmonella grow on plant surfaces that would otherwise be inhospitable.

On the practical side, notes Barak, farmers can now add these insects to the list of risk factors they consider when making crop management decisions.

“Now when a raw-produce grower looks out and it’s been a bad year for insect infestation, it might sig- nal to them that they may have a higher food safety risk,” she says.

Five things everyone should know about . . . Milkweed

1. It is the stuff of life for monarch butterflies. Monarchs lay their eggs on milkweed, and milkweed leaves serve as nearly the sole food of monarch caterpillars. But many species benefit from the bounty of milkweed. Milkweed flowers produce nectar that other kinds of butterflies, honey bees, native bees and other pollinators enjoy. Hummingbirds line their nests with floss from milkweed seed pods.

2. It’s both medicine and poison. Milkweeds—there are more than 100 species—belong to the genus Asclepias, named after the Greek god of medicine and healing. Milkweeds have been used in medicine for thousands of years because their tissue contains cardiac glycosides, which increase the heart rate and in a purified form are useful in treating such conditions as cardiac arrhythmia and congestive heart failure. As a crude extract, cardiac glycosides are toxic and have been used as poison. Monarch larvae retain the toxins they consume in milkweed leaves and as butterflies remain toxic to predators.

3. Its presence is dwindling, along with the monarchs. The first decade of this century saw a 58 percent decline in milkweeds in the Midwest, according to a 2012 study—a time when we’ve also seen a whopping 81 percent decrease in monarch production. Factors often cited for milkweed’s decline include loss of habitat as grasslands and conservation reserves have been converted to farmland for corn and soybeans as well as increased use of herbicides on those crops.

4. There’s a growing movement to bring it back. Researchers at CALS and elsewhere have noted an increase in biodiversity, pollination and other ecosystem services that come from establishing or maintaining a mix of perennial native plants near cropland—and milkweed, they say, should be part of it. Vigorous efforts are taking place throughout the Midwest to plant large areas of milkweed along the monarchs’ migration path to Mexico, where they spend the winter.

5. Milkweed will enliven and beautify your garden—but keep your gloves on when handling. The toxins that protect the monarch can harm humans. Make sure the sap doesn’t get into your eyes, and if it does, seek medical attention as it can cause significant damage. While not all milkweeds are equally toxic and some kinds can be eaten, great care must be taken when selecting and preparing it.

 

Five things everyone should know about gluten

1. What is it? Gluten is a substance composed of two proteins—gliadin and glutenin—that are found in the endosperm (inner part of a grain) of wheat, rye, barley and foods made with those grains, meaning that gluten is widespread in a typical American diet.

2. Is it harmful? People who suffer from celiac disease, an autoimmune digestive disorder, are unable to tolerate gluten. Even a small amount of it (50 milligrams) can trigger an immune response that damages the small intestine, preventing absorption of vital nutrients and potentially leading to other problems such as osteoporosis, infertility, nerve damage and seizures.

3. How widespread is celiac disease? An estimated 1.8 million Americans have celiac disease; as many as 83 percent of those suffering from it remain undiagnosed or are misdiagnosed with other conditions. Another 18 million (about 6 percent of the population) do not have celiac disease but suffer from gluten sensitivity. They report such symptoms as diarrhea, constipation, bloating and abdominal pain—which also are symptoms of celiac disease—but do not experience the same intestinal damage. For those with celiac disease or gluten intolerance, a gluten-free diet is beneficial.

4. Should you cut gluten from your diet even if you don’t have these conditions? Probably not. Restriction of wheat in the diet often results in a decrease in the intake of fiber at a time when most Americans consume significantly less than the recommended amount. Low-fiber diets are associated with increased risk of several acute gastrointestinal diseases (examples: constipation, diverticulosis) and chronic diseases such as heart disease and colon cancer. If not done carefully, gluten-free diets also tend to be low in a number of vitamins and minerals.

5. Don’t diagnose yourself. The broad range of symptoms associated with celiac disease and gluten sensitivity may be due to other causes; self-diagnosis and treatment of perceived gluten intolerance may delay someone from seeking more appropriate medical care. The only way to know for certain if you have celiac disease is from a blood test for the presence of specific antibodies followed by a biopsy of the small intestine. If you are experiencing the symptoms described above, please seek medical care.

Beth Olson is a professor of nutritional sciences. Her principal research areas concern breastfeeding support and improving infant feeding practices in low-income families.

Upping the Orange

Sherry Tanumihardjo is a CALS professor of nutritional sciences and director of the Undergraduate Certificate in Global Health, a popular new program that draws participants from majors all across campus. She has almost three decades of experience working with vitamin A, and her research team has conducted studies in the United States, Indonesia, South Africa, Ghana, Burkina Faso and Zambia. Tanumihardjo has acted as a consultant to many studies throughout the world to assist with study design and appropriate standardization. She is a strong advocate for the promotion of nutritionally enhanced staple foods, vegetables and fruits to enhance overall health and well-being.

Describe your work with orange vegetables.
I have worked for a number of years on carrots of many colors as well as on orange-flesh sweet potato and, more recently, orange maize. Basically we are trying to improve the vitamin A status of individuals by having them consume more orange fruits and vegetables in general.

Can you give us an idea of how you go about doing that?
For many years I have worked with carrot breeder Phil Simon in the Department of Horticulture. He was breeding carrots for more orange color. We did a series of studies in both an animal model and in humans, trying to look at the uptake and distribution of the carotenoids that give the vegetables their orange color—and the vitamin A that is made from the carotenoids. Then we moved on to orange vegetables in humans in Africa. I have worked with orange-flesh sweet potato in South Africa and with orange maize in Zambia.

Can you describe the connection between the color and the nutritional value?
There are three well-known precursors of vitamin A that are called pro-vitamin A carotenoids. Those are beta-cryptoxanthin, alpha-carotene and beta-carotene. Many of you may have heard of beta-carotene because it is one of the compounds found in many over-the-counter supplements. But those are also the compounds that give carrots and orange maize their bright orange color.

What happens if there is not enough vitamin A in the diet?
The most drastic thing that can happen is death. So we go around trying to get people to improve their vitamin A intake not only to prevent death—there are many steps before that happens, and one of them is blindness. Vitamin A is extremely important in vision and it also helps us ward off disease, so it’s a very important vitamin.

How did you get started in Africa?
It actually started very slowly. I used to be a consultant and I would fly back and forth to different countries to help them look at study design. The sweet potato study was funded by the International Potato Center. I helped them design the study, they did the school implementation—a feeding study—and then I helped them get the work published. My work with orange maize started in 2004 in collaboration with HarvestPlus, a project managed by the International Food Policy Research Institute. We started working with animal models and then progressed to full-fledged feeding trials, the latest of which we finished in 2012.

What were some of the challenges in your work in Africa?
The challenge is that feeding trials, if they’re going to show what we call efficacy, have to be highly controlled. So that means you have to keep the children for long periods of time and feed them all of the foods—and the foods need to be the same across the group except your test food. So in South Africa we fed orange-flesh sweet potato to half the children and white-flesh sweet potato to the other half. And then when we moved on to orange maize we did two studies. One study was similar to the sweet potato study where we fed white maize and orange maize. And then we did a second study where we had three groups, which got a little more complicated. We had white maize, orange maize and then white maize with a vitamin A supplement.

Another challenge is that all of the human work that I do involves blood—so we have to take blood from these children. Vitamin A in the human body is stored in the liver, and we use indirect markers of liver reserves of vitamin A that you can pick up from the blood.

Looking down the road what kind of goals do you have for your research?
We would like for people to have optimal health by having a diet that has not only all the nutrients you need but also some of the potential compounds that gear us toward optimal health. So it’s not just about fighting blindness anymore, but to see if we can get people into a new nutritional state where they are actually able to ward off diseases such as cancer.

What kind of progress have you made?
We have had significant progress with sweet potato. Most people in Africa used to eat white sweet potato, not the orange sweet potato we eat here in the United States. Many countries in Africa have now adapted the vines to be orange-flesh sweet potatoes. We think that’s a success story. Regarding orange maize, there are three lines of orange maize that have been released by the Zambian government. Currently orange maize is available to consumers. Right now it’s at a premium price, but hopefully with time the price will come down to the level of white maize.

How did you get interested in this line of work?
It chose me. It wasn’t something that I was looking for, but I was working with vitamin A and if you’re working with vitamin A and status assessment, it’s going to draw you to the countries that may have a history of vitamin A deficiency.

Can you talk a little more about the international nutritional programming you’ve been involved in?
Most of the work that I’ve done is to support biochemical labs. We have not done a lot of nutrition education on the ground, although that is a goal of mine, especially in Zambia. We have discovered that Zambians actually have really good sources of vitamin A in their daily diets, so we want to help them continue to eat the fruits and vegetables that are good sources of those phytonutrients and vitamins and minerals.

The other thing that I work on is isotope methods, which sounds a little scary!

What are isotope methods and what do they do?
We work with a compound called 13C. Typical carbon in the human body is 12C and radioactive carbon is 14C. We are working with the form of carbon that constitutes 1 percent of the human body. It’s perfectly safe to use, but it also has allowed me to work with the International Atomic Energy Agency. That’s the same agency that oversees radioactive bombs in different countries, so it’s kind of interesting that they have something called Atoms for Peace. And they actually received the Nobel Peace Prize one year based on the safe use of isotopes in nutrition.

I have worked in several countries trying to help them understand isotope methods and to apply isotope methods at the population level to inform public health policy. It’s a very technical method, but it can answer questions of public health significance.

So it’s a research tool. And what kinds of questions does it answer?
It is the most sensitive marker of liver reserves of vitamin A. Basically what we do is we give a dose of vitamin A that has a slightly higher amount of 13C than what’s found naturally in the environment, and then we can follow the uptake and the clearance of that 13C in the human body. And from that we can calculate total body stores of vitamin A—how much is in the whole body.

To conclude here, there’s an interesting story about your office and a more recent career development of yours—serving as director of the Undergraduate Certificate in Global Health, a program you helped develop and launch in 2011.
Yes. The Nutritional Sciences Building was originally a children’s hospital, and this particular office that I sit in sat idle for many, many years, used only for small committee meetings and things like that. When we received funding for the Undergraduate Certificate in Global Health, I looked in this office again and realized that it now fits my purpose. Originally it was the viewing room for children who had died from a variety of diseases, and the parents would sit in this room and mourn their lost child. I decided that this room fit my new mantra at the university, which is to empower undergrads, to mobilize them, to try to change the world. And while I’m sure we won’t have 100 percent participation, we’ve already had about 1,000 students go through the program.

The Mysteries of RNA

For people who know about RNA mostly from its place in the central dogma of biology—DNA➙RNA➙Protein—this story may hold a number of surprises.

That handy equation, taught in Biology 101 courses around the globe, sums up the flow of genetic information in living organisms: how our DNA gets copied into RNA, which then gets converted into proteins, the building blocks of our cells, our bodies.
Originally, the RNA referred to in this equation—messenger RNA, or mRNA, the type that codes for proteins—was the only kind known to science. However, over the years, it has become clear that there are many, many other kinds.

“The world of RNA has proven to be a big and fascinating place,” says Marv Wickens, a CALS professor of biochemistry and leading pioneer in RNA research. “I’ve come to think of it as a Fellini movie, full of strange and unexpected characters.”

These Felliniesque characters are all the non-coding RNAs that exist in nature—the kinds that don’t code for proteins. They go by names like small interfering RNA, piwi-interacting RNA, microRNA, long non-coding RNA, small nuclear RNA—the list goes on and on. Together they far outnumber messenger RNAs in the cell; while only 3 percent of the human genome gets made into proteins (via messenger RNA), a full 80 percent gets copied into RNA.

What are all of these other RNAs doing? Lots of important and surprising things, scientists are discovering.

Over the past few decades, RNA, a close chemical cousin of DNA, has proven itself to be a much more versatile molecule than originally thought—far more than just a passive messenger.

The first big surprise came in the 1980s when it was shown that RNA can have catalytic activity, meaning that it can perform chemical reactions inside the cell. Originally assumed to be inert, like DNA, scientists found RNA molecules that could edit their own sequence—expunging a segment of their own genetic code.

Later, RNAs were discovered at the heart of important cellular machines, or enzymes, performing critical catalytic reactions, including those at the heart of the cell’s information transfer system. Previously only proteins were thought capable of such enzymatic feats.

Creating a Healthier World

YOU CAN’T SPOT THEM RIGHT AWAY—they’re hidden in plain sight, often disguised as majors in the life sciences—but there are thousands of undergraduates on the University of Wisconsin–Madison campus who, in terms of their future careers, consider themselves “pre-health.”

What are their reasons? For some students, the motivation is acutely personal. As a child, Kevin Cleary BS’13 (biology) felt an urgent need to help as he watched his father deal with recurrent brain tumors. “By age 11, I knew I had a future in health care,” says Cleary. Many others aren’t yet sure what role they will play, but they are eager for guidance on how to use their majors to address an array of global problems including hunger, disease, poverty and environmental degradation. Says senior biochemistry major Yuli Chen, “I want to make an impact on people, and I believe that every person has the right to be provided basic necessities such as clean water, education and food.”

For much of the past century, young people seeking to address health-related suffering may have felt relatively limited in their options. Most considered medical school (still the gold standard to many), nursing school or other familiar allied health occupations that are largely oriented toward addressing disease after it occurs.

In recent years, however, health experts worldwide have placed an increasing emphasis on the importance of prevention in achieving health for the largest possible number of people. This was illustrated at UW–Madison in 2005, when the University of Wisconsin Medical School changed its name to the School of Medicine and Public Health, offering the following reason: “Public health focuses on health promotion and disease prevention at the level of populations, while medicine focuses on individual care, with an emphasis on the diagnosis and treatment of disease. Ideally these approaches should be seamlessly integrated in practice, education and research.”

The founding in 2011 of the interdisciplinary Global Health Institute (GHI), a partnership of schools, colleges and other units across campus, broadened the university’s approach to health still further:

“We view the health of individuals and populations through a holistic context of healthy places upon which public health depends—from neighborhoods and national policies to the state of the global environment. This approach requires collaboration from across the entire campus to address health care, food security and sustainable agriculture, water and sanitation, environmental sustainability, and ‘one health’ perspectives that integrate the health of humans, animals and the environment.”

Demand by UW students for educational options built around this broad concept of health had been growing for some time. Before the creation of the GHI, an Undergraduate Certificate in Global Health was introduced to offer students an understanding of public health in a global context. The certificate explores global health issues and possible solutions—and shows students how their own majors and intended professions might make those solutions reality. Although administered from CALS and directed by CALS nutritional sciences professor Sherry Tanumihardjo, the certificate accepts students from across campus and highlights ways in which teachers, engineers, farmers, social workers, journalists, nutritionists, policy makers, and most other professions can play a role in global health. Funding is provided through the Madison Initiative for Undergraduates, grants and private donations.

Earning the certificate requires completion of core courses focusing heavily on agriculture and nutrition, the importance of prevention and population-level approaches in public health, and the role of the environment in health. Students also complete relevant electives (examples: women’s health and human rights, environmental health, international development), and—most transformative for students—a field course, usually a one- to three-week trip either abroad or to a location in the United States where a particular global health issue is being addressed by one or more local partner organizations in ways specific to the place and the people who live there.

Stopping Multiple Sclerosis

A diagnosis of multiple sclerosis (MS) is a hard lot. Patients typically get the diagnosis around age 30 after experiencing a series of neurological problems such as blurry vision, a wobbly gait or a numb foot.

From there, this neurodegenerative disease follows an unforgiving course. People with severe cases are typically bed-bound by age 60. Current medications don’t do much to slow the disease, which afflicts around 400,000 people nationwide, with 200 new cases diagnosed each week.

Now a team of CALS biochemists has discovered a promising vitamin D–based treatment that can halt—and even reverse—the course of the disease in a mouse model of MS. The treatment involves giving mice exhibiting MS symptoms a single dose of calcitriol, the active hormone form of vitamin D, followed by ongoing vitamin D supplements in their diet.

“All of the animals just got better and better, and the longer we watched them, the more neurological function they regained,” says CALS biochemistry professor Colleen Hayes, who led the study and published her team’s findings in the Journal of Neuroimmunology.

While scientists don’t fully understand what triggers MS, some studies have linked low levels of vitamin D with a higher risk of developing the disease. Hayes has been studying this “vitamin D hypothesis” for the past 25 years. She and her researchers have revealed some of the molecular mechanisms involved in vitamin D’s protective actions, and also explained how vitamin D interactions with estrogen may influence MS disease risk and progression in women.

In the current study, funded by the National Multiple Sclerosis Society, Hayes’ team compared various vitamin D–based treatments to standard MS drugs. In each case, vitamin D–based treatments won out. Mice that received them showed fewer physical symptoms and cellular signs of disease.

Hayes’ team compared the effectiveness of a single dose of calcitriol to that of a comparable dose of a glucocorticoid, a treatment now in use. Calcitriol came out ahead, inducing a nine-day remission in 92 percent of mice on average, versus a six-day remission in 58 percent for mice that received glucocorticoid.

“So, at least in the animal model, calcitriol is more effective than what’s being used in the clinic right now,” says Hayes.

But calcitriol can carry some strong side effects—it’s a “biological sledgehammer” that can raise blood calcium levels in people, Hayes says. After experimenting with various doses, her team arrived at a regimen of a single dose of calcitriol followed by ongoing vitamin D supplements in the diet. This one-two punch “was a runaway success,” she says. “One hundred percent of mice responded.”

While she is excited about the prospect of her research helping MS patients someday, Hayes is quick to point out that it’s based on a mouse model. The next step is human clinical trials. A multicenter clinical study is currently being designed. If trials are successful, people experiencing those first warning signs—the wobbly gait, the numb foot—could receive the new treatment and stop the disease in its tracks.

“It’s my hope that one day doctors will be able to say, ‘We’re going to give you an oral calcitriol dose and ramp up the vitamin D in your diet, and then we’re going to follow you closely over the next few months. You’re just going to have this one neurological episode and that will be the end of it,’” says Hayes. “That’s my dream.”

Meat, With a Touch of Fruit

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

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

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

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

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

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

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

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

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

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

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

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

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?”

Targeting a Killer

By the time doctors diagnose septic shock, patients often are on a knife’s edge. At that point, for every hour that treatment is delayed, a person’s risk of death rises an alarming six percent.

Time is of the essence. And CALS animal sciences professor Mark Cook was part of a team that developed a breath biomarker technology capable of detecting septic shock 12 to 48 hours earlier than standard methods. This powerful device, which was patented in 2008 and is making its way through clinical trials, creates an exciting opportunity for new, life-saving medical interventions.

“If you can detect septic shock earlier, then you can begin to explore ways of treating it earlier,” says Cook, who already is in the process of developing a promising antibody-based treatment.

Septic shock—or severe sepsis—affects approximately 750,000 people in the United States each year, taking more than 200,000 lives and costing around $17 billion in treatment.

It occurs when a person’s immune system, spurred by a bacterial infection or serious physical trauma, launches a massive inflammatory response that can lead to a drop in blood pressure, multiple organ failure and death.

The gastrointestinal tract is believed to be the primary site of this runaway response. Because of that, some scientists call the gut “the motor for sepsis,” says Cook. So it’s no surprise that Cook looked to the gut for a solution.

With funding from a Robert Draper Technology Innovation Fund grant from the UW–Madison Graduate School, he began working to interfere with the activity of a protein called sPLA2, which is part of the chain of events in the gut that drives septic shock. It is a dual-purpose protein that can act as both an enzyme and a signaling molecule, so it wasn’t initially clear which of the protein’s roles—enzyme, signaling or both—were involved.

Cook and Jordan Sand, a scientist in Cook’s lab, decided to first try blocking the gut protein’s ability to signal, guessing that this would calm the immune response. So Sand made a series of antibodies that inhibited sPLA2’s signaling function—but not its enzyme function—and then tested them in a mouse model of septic shock.

“We actually made it much worse,” says Sand. “We absolutely failed. There’s no other way to say it.”

Sand went back and made antibodies that blocked only the protein’s enzyme function. Those worked. “We had 100 percent survival across the board,” says Sand.

If the antibody approach also works in people, this treatment could help patients with septic shock stay alive while they wait for antibiotics and other standard treatments to kick in.

Cook and Sand have filed a patent on the technology. But, Cook notes, “There are still a lot of steps to get this into human medicine.”

Tasty Solution

After having a stroke in 2008, Jan Blume lost the ability to swallow for two full years. As she slowly regained that vital function, she faced a new challenge: drinking the thickened beverages that are recommended for people with swallowing problems, or dysphagia. She found the drinks almost intolerable.

“They taste bad and the texture is so weird,” recalls Blume, a retired nurse living in Appleton who can now eat and drink whatever she wants. “At some point, I would have just stopped using them—and either done okay or developed problems.”

Fortunately there may soon be a better beverage option for people with swallowing problems, thanks to collaboration between a dysphagia specialist at the UW–Madison School of Medicine and Public Health—and a candy expert at CALS.

It started by chance when JoAnne Robbins, head of the medical school’s Swallowing, Speech and Dining Enhancement Program, asked CALS food scientist Rich Hartel if she could borrow his viscometer, a device that measures viscosity, or the thickness of fluids.

“After learning that one of Rich’s areas of expertise was chocolate, I mentioned that there are all these awful-tasting drinks made for people with swallowing problems, and nothing in chocolate,” recalls Robbins, a professor of medicine with an affiliate position in the CALS nutritional sciences department. “So we decided to develop a thickened chocolate drink together.”

The biomechanical events of swallowing are complex, involving 40 sets of muscles. Many things—including injury, illness and natural muscle atrophy due to aging—can cause dysphagia, which afflicts some 18 million adults in the United States.

The condition can be embarrassing. Some people with dysphagia simply stop going to restaurants or even eating with their families at home due to the struggle to swallow or the length of time it takes them to finish a meal. “This can have a devastating impact on social structures,” says Robbins.

But it’s more than just a quality-of-life issue, notes Robbins. Dysphagia can cause dehydration, hunger and malnutrition. Worse, if people with dysphagia aspirate liquids or food into their lungs, it can lead to pneumonia—and possibly death.

Many patients with dysphagia are advised to drink thickened beverages, which tend not to leak into the airway. But these products often leave much to be desired, and not just because of a bad flavor.

“The commercial products that are out there don’t match the diagnostic standards. So people think they’re buying a ‘nectar thick’ beverage, which is supposed to be a certain viscosity, but it’ll turn out that it’s not even close,” says Hartel.

That’s where Hartel and Robbins figured they could help: by developing what they call “bio-
physically based fluids” that match the diagnostic standards—making them safer for patients to drink—and that also taste good.

With the support of a U.S. Department of Agriculture grant, Hartel analyzed 15 thickeners and developed beverages using a handful of them. Robbins tested the drinks for safety in her patients, and a third team member, University of Minnesota researcher Zata Vickers, gathered key sensory data.

Ultimately the team gave up on chocolate after reading a number of studies showing that citrus flavors elicit a faster, better swallow. They are in the process of patenting their beverage technology through the Wisconsin Alumni Research Foundation, and are excited for the day when people who must drink thickened beverages—as Jan Blume did—will have a safer, tastier option.

“I’m in this to make my patients feel better,” says Robbins. Of her CALS collaborator Robbins says, “Rich is a very good partner. He was open to expanding the focus of his research program. He liked the idea of helping people directly.”

Gut Feeling

Students at a Chicago public high school got some hands-on—and hands-in—experience with two cannulated cows that CALS dairy science management instructor Ted Halbach and dairy science PhD student Shane Fredin brought down to the Windy City.

Although the Chicago High School for Agricultural
Sciences (CHSAS) is a magnet school for ag and life sciences, its urban location limits student opportunities to get up close and personal with farm animals. The cows were part of a workshop teaching students how feed is digested in the four compartments of a dairy cow’s stomach.

“The students were stunned that they got to put their arm in a cow,” notes CHSAS instructor Maggie Kendall. “After the first brave soul, they all lined up with gloves, eager to follow suit. They were enthralled and it was organized in a way that kept their attention. They had just enough time at each station to absorb the material and ask questions.”

CALS regularly recruits students from CHSAS, sparking interest and cultivating relationships through such activities as workshops and frequent visits by Tom Browne, CALS assistant dean for minority affairs. Currently five students from CHSAS are undergrads at CALS.