Class Act: Energizing the Classroom

When biochemistry senior Hong-En Chen first got involved with a student organization called Energy Hub, she knew she could bring something special to the table.

As the daughter of a preschool teacher, she’d interacted a lot with young children throughout her own childhood and adolescence. While in high school she worked as a teacher and tutor in music, math and reading in both English and Mandarin at the Einstein School in Madison, a private preschool and after-school enrichment center for elementary school students.

Based on her experience, she saw an important niche for Energy Hub: The group could go out to local elementary schools and hold after-school classes about energy.

“When kids are young, they’re like sponges. They absorb a lot of information and are enthusiastic learners,” notes Chen. “When we introduced concepts about energy use, conservation and sustainability, the kids impressed us not only by handling complex material, but also by applying ideas to their everyday lives.”

As outreach director of Energy Hub, Chen got other club members on board to pilot their project, working with second- to fifth-grade students at four Madison elementary schools. Based on that experience, they applied for and received a Wisconsin Idea Fellowship grant to further develop their curriculum during the 2012–2013 school year. They created a 10-week program that is going strong this year.

Hands-on activities are key, says Chen, whether using an educational science toy like Snap Circuits to teach the concepts behind powering lights and fans, or having students divide into the fantasy cities of Greenville and Coaltown to talk about how they, as residents, would use energy from various sources to get through a day. “It was a fun way to get them thinking about the costs and benefits of renewable versus nonrenewable energy sources,” Chen says.

Chen’s thinking a lot about that topic herself. She is researching compounds for solar energy conversion in chemistry professor Song Jin’s lab. And she is considering graduate programs in materials chemistry with an eye toward working in renewable energy research.

Learn more about Energy Hub at www.uwehub.org.

Will Dead Species Live Again?

Stanley A. Temple is the Beers-Bascom Professor Emeritus in Conservation in forest and wildlife ecology at CALS and a former chair of the conservation biology and sustainable development program at the Gaylord Nelson Institute for Environmental Studies. For 32 years Temple occupied the faculty position once held by Aldo Leopold, and while in that position he received every University of Wisconsin teaching award for which he was eligible. Since his retirement from academia in 2008 he has been a Senior Fellow of the nonprofit Aldo Leopold Foundation. He and his 75 graduate students have worked on conservation problems in 21 different countries and have helped save some of the world’s rarest and most endangered species. Last spring Temple gave a TED talk at a special event devoted to de-extinction, a concept that has captured the imagination of scientists and the general public alike.

What is “de-extinction”?
De-extinction is a recent term that involves bringing back an extinct species using DNA that’s been recovered from preserved material. There are two ways that it can be accomplished: one would be cloning to produce a copy of an extinct individual’s genome. The second way is through genetic engineering to re-create a close approximation of what the extinct species’ genome might have once been. The reality is that it’s no longer science fiction. We’re getting close to being able to revive extinct species from recovered DNA.

This must make for some unusual scientific partnerships.
It’s an interesting synthetic endeavor that matches the biotechnologists in the laboratory with conservationists in the field. The biotech crowd will be responsible for recovering DNA from an extinct species and through either cloning or engineering turning that DNA into individuals. But once they’ve done that, the next step involves people like myself who know how to recover endangered species by taking a small number of individuals and turning them into a viable population and getting them back into the wild.

What opportunities might this technology present to conservation efforts?
On the plus side, obviously, it would be exciting to bring back a species that human beings drove to extinction. But even if we weren’t able to do that, the technology presents an appealing opportunity to recover DNA from preserved specimens of an endangered species and use it to enhance the genetic diversity of the surviving population.

Can you please elaborate on that?
Conservationists have recovered many endangered species from very low population levels and saved them from extinction. The problem is, they’re often genetically depauperate, or lacking in genetic diversity. If we can recover some of the lost genes from preserved specimens collected before the population crashed, we might greatly improve the species’ prospects for long-term survival.

How would a conservation biologist go about actually applying this?
De-extinction is still an unproven concept, but it’s likely that sometime in the coming decades it will happen. Once they have revived individuals of an extinct species in the lab, then conservation biologists could try to recover the species by captive breeding and reintroducing the species to the wild. But conservation biologists get concerned about some of the details: Which species are going to be revived? Are they the right species? Are they the species that have the best chances for long-term survival in the world today? Are they species that might actually enhance the ecological health of the ecosystem that they were once part of, like the wolves reintroduced to the Yellowstone ecosystem? These are all questions of setting priorities for which species to actually revive.

How would you recommend setting priorities?
As a conservation biologist I would certainly look first at recently extinct species that were affected by a threat we’ve now overcome. Not only are those the ones for which we’re likely to have good quality DNA, but their ecological niche in the wild hasn’t been vacant for very long. And as a result, the ecological community that they were once part of has not readjusted itself to their absence, and might once again easily accommodate the species in its midst. On the other hand, if you’re dealing with a species that’s been extinct for a very long period of time—centuries or even millennia—the ecosystem that they were part of has moved on, and a species like that, once back in the system, could essentially be the equivalent of an invasive species. It might disrupt the system and threaten extant species.

How would you like to see this development proceed?
Considering the timeline that we probably have years or even decades to do this right—I and other individuals and groups that are thoughtful and somewhat skeptical about this would like to see a very broad discussion of the implications. We would like to see a lot of input in deciding the priorities about which species to bring back. We would not like to see this done in secret, which, unfortunately, is where this seems to be heading. This very expensive work is not receiving government funding and doesn’t have any sort of public oversight. Hence, privately funded biotech labs seem to be focusing on reviving spectacular extinct species, like mammoths and other Ice Age animals, rather than species that have a real chance of surviving in today’s world.

What would be an important takeaway point for the general public?
De-extinction doesn’t mean we can ignore the significance of extinction—to think, “Oh well, we can let species go extinct because we can always save some DNA and bring them back later.” This would just be an open door for activities that have been constrained by concerns for biodiversity and basically give the green light to go ahead and precipitate extinctions of species that are already with us.

The Value of GMOs

For all the discussion surrounding genetically modified foods, there have been strikingly few comprehensive studies that put a numeric value on the costs and benefits.

Now there’s more to talk about.

By analyzing two decades’ worth of corn yield data from Wisconsin, a team of CALS researchers has quantified the impact that various popular transgenes have on grain yield and production risk compared to conventional corn. Their analysis, published in Nature Biotechnology, confirms the general understanding that the major benefit of genetically modified (GM) corn doesn’t come from increasing yields in average or good years—but from reducing losses during bad ones.

“For the first time we have an estimate of what genetically modified hybrids mean as far as value for the farmer,” says CALS and UW-Extension corn agronomist Joe Lauer, who led the study.

Lauer has been gathering corn yield and other data for the past 20 years as part of the Wisconsin Corn Hybrid Performance Trials, a project he directs. Each year his team tests about 500 different hybrid corn varieties at more than a dozen sites around the state, with the goal of providing unbiased performance comparisons of hybrid seed corn for the state’s farmers. When GM hybrids became available in 1996, Lauer started including them in the trials.

“It’s a long-term data set that documents one of the most dramatic revolutions in agriculture—the introduction of transgenic crops,” says Lauer, who collaborated with CALS agricultural economists Guanming Shi and Jean-Paul Chavas to conduct the statistical analysis, which considered grain yield and production risk separately.

Grain yield varied quite a bit among GM hybrids. While most transgenes boosted yields, a few significantly reduced production. At the positive end of the spectrum was the Bt for European corn borer (ECB) trait. Yield data from all of the ECB hybrids grown in the trials over the years showed that ECB plants out-yielded conventional hybrids by an average of more than six bushels per acre per year. On the other hand, grain yields from hybrids with the Bt for corn rootworm (CRW) transgene trailed those of regular hybrids by a whopping 12 bushels per acre. But even among poor-performing groups of GM corn, there are individual varieties that perform quite well, Lauer notes.

Where transgenic corn clearly excels is in reducing production risk. The researchers found that every GM trait package—whether single gene or stacked genes—helped lower variability. For farmers, lower variability means lower risk, as it gives them more certainty about the yield levels they can expect.

Lauer equates choosing GM crops with purchasing solid-performing, low-risk stocks. Just as safe stocks have relatively low volatility, yields from GM crops don’t swing as wildly from year to year, and most important, their downswings aren’t as deep.

GM crops help reduce downside risk by reducing losses in the event of disease, pests or drought. Economists Shi and Chavas estimated the risk reduction provided by modified corn to be equivalent to a yield increase ranging from 0.8 to 4.2 bushels per acre, depending on the variety.

Risk reduction associated with GM corn can add up to significant savings for farmers—as much as $50,000 for 1,000 acres, calculates Lauer. “It depends on the price that farmers can receive for corn,” he says.

But the two factors quantified in this study—yield and production risk—are just part of the overall picture about GM crops, says Lauer. He notes there are other quantifiable values, such as reduced pesticide use, as well as ongoing concerns about the safety and health of growing and eating genetically modified foods.

“There’s a lot of concern about this biotechnology and how it’s going to work down the road,” says Lauer, “yet farmers have embraced it and adopted it here in the U.S. because it reduces risk and the yield increases have been as good as—or some would argue a little better than—what we’ve seen with regular hybrid corn.”

Getting to the heart of a problem

When Marion Greaser set out to study titin, the largest natural protein known to man, his goal was to answer some basic questions about its role in the body. A major protein of skeletal muscle that’s also found in heart tissue, titin gives muscle its elasticity and is known for its massive size, which ranges from around 27,000 to 33,000 amino acid residues in length.

“Initially we were just going to look at whether titin was related to muscle growth in animals,” says Greaser, a CALS professor of animal sciences.

Working in rats, his team looked at changes in the size of the titin protein over the course of animal development—and immediately came across something strange. In most cases the titin protein shifted from a larger form to a smaller form during development due to natural changes in protein processing known as alternative splicing. But in some rats the titin didn’t change. It stayed big.

The team wondered if they’d mixed up the samples. “But we’d kept good track of things and, in fact, all of the weird samples were from the same litter of rats,” says Greaser. “Then the light bulb went off: There must be some genetic reason why these samples are different. These rats had a genetic mutation affecting the alternative splicing of the titin.”

But where was the mutation? They first checked the titin gene itself, but it was fine. With hard work, they were able to pinpoint the mutation to a little-studied gene called RBM20, which had been previously linked to dilated cardiomyopathy and sudden death in humans.

Dilated cardiomyopathy affects approximately one in 2,500 people. Sufferers have enlarged hearts, with thin walls, that don’t pump blood very well. People with the RBM20 mutation need heart transplants and, without them, tend to die quite early: between ages 25 and 30.

Scientists first linked RBM20 to hereditary dilated cardiomyopathy in 2009, but they hadn’t yet figured out how a faulty RBM20 gene worked—or didn’t work—to cause disease inside the body.

Greaser’s accidental discovery, as described in Nature Medicine, filled in the blank. In healthy individuals, the RBM20 protein is involved in the alternative splicing that helps trim titin down to its smaller, adult form. Without it, titin doesn’t get processed correctly, and the presence of extra-large titin in heart tissue leads to disease.

“Now doctors can analyze people showing symptoms of dilated cardiomyopathy, see if they’re carrying this mutation and factor this information into their treatments,” says Greaser. That treatment would probably start with careful monitoring to catch any further deterioration of the heart condition, Greaser notes.

Tech Transfer Showcase

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

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

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

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

Deltanoid

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

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

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

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

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

TRAC Microbiology

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

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

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

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

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

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

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

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

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

Krishna Ella

Not everyone manages to realize his grandest dream, but Ella is well on his way. After studying and working in the United States, Ella returned to his native India vowing to fight the spread of infectious diseases in developing countries. In 1996, he and his wife, Suchitra, founded Bharat Biotech with the goal of producing vaccines for diseases such as hepatitis and typhoid for pennies on the dollar. Bharat has supplied more than 1 billion vaccine doses to Asia, Africa and Latin America, and the company has two grants from the Bill and Melinda Gates Foundation to develop affordable vaccines for malaria and rotavirus. Meanwhile, Ella has emerged as one of his country’s strongest advocates for research and development. He says his dream is to connect UW-Madison with India to act as a catalyst for its agricultural economy. One way he’s working toward that goal is by paving a route for Indian science students to study at the UW through the new Khorana Scholars exchange program.

Jeff Browning

As senior director of immunobiology research at Boston-based Biogen Idec, Browning has presided over the development of several new pharmaceutical drugs. One success story gives him particular satisfaction. Earlier in his career, Browning co-discovered the surface form of lymphotoxin, an important signaling chemical in the human body. The discovery led to the development of Baminercept, an early-stage drug designed to treat rheumatoid arthritis. Biogen is currently ushering this drug through human clinical trials, and scientists there are optimistic it will work to treat other autoimmune diseases as well.

Youth Movement

As a lab assistant in CALS’ Center for Eukaryotic Structural Genomics, Stuart Ballard performs tasks typical of an upper-level graduate student: sonicating cells, cleaving proteins and running gas chromatography trials.

But Ballard isn’t a graduate student. He’s a senior at Madison West High School who’s still shy of his 18th birthday.

Baby-faced researchers such as Ballard are becoming a common sight around UW-Madison, which increasingly is trying to cultivate budding young scientists before they even arrive on campus. Through arrangements such as the Youth Apprenticeship Program, a state-run project that matches promising high-school students with practical experiences in their desired careers, CALS labs have employed dozens of science-minded high-school students the past decade.

For students such as Ballard, who is enrolled in YAP’s biotechnology thrust, the program offers a taste of working science that high school just can’t replicate.

“Working in the research lab is amazing,” says Ballard, who plans to pursue both an M.D. and Ph.D. after college. “It’s meaningful. In high school, you do your labs and it’s not contributing to human knowledge in any way.”

Students in the program attend weekly evening training sessions to master basic lab techniques such as using pipettes, running gels and handling biohazardous material. Once paired with a professional mentor, they spend 10 to 15 hours per week working in the lab. They get paid for their labor, which involves much more than washing dishes.

“They get a bench just like everybody else,” says entomology professor Que Lan, who has had youth apprentices in her lab for seven years. “They get the same treatment as my graduate students. I work with them one on one. I help them solve problems.”

Lan says nearly all of her apprentices have gone on to study science as college students, a reward that compensates the time mentors invest working with the young students.

“Kids always associate science with either (being) very smart or very nerdy,” she says. “I think I’m trying to show them, ‘Yes, you can have a career; yes, you can have a family; and yes, you can have fun.'”

“It’s been a very nice program to be involved in,” adds biochemistry professor Brian Fox, who is mentoring Ballard and three other apprentices. “Once they get comfortable with the techniques, they turn out to be very helpful employees.”

Under Fox’s tutelage, Ballard has learned how to purify proteins while formulating ideas for his own future research. He has helped train undergraduate students as lab assistants, and he was recently offered an opportunity to work as a volunteer in a second lab on campus.

While those commitments can make for a demanding schedule—Ballard is only at his high school for a single weightlifting class—he says the experience is incomparable. Asked if he feels like he’s missing out on a normal high-school experience, he laughs, “Not at all, not at all.”

Coming Off the Bench

After graduating with a bachelor’s degree in genetics, Heather Gerard BS’00 took a good position in a campus lab. Yet she couldn’t help worrying about her future.

“I didn’t want to be a bench scientist my whole life,” says Gerard, who now works as a patent liaison at the Madison-based biotech firm Promega. “But I was totally oblivious to what else was out there.”

To find out, she joined UW-Madison’s Master’s of Science in Biotechnology program, which aims to help young professionals navigate the complex world of biotechnology. Begun in 2004, the two-year program doesn’t teach science as much as it does business acumen—one of the clear signs that biotechnology is establishing itself as more than just a scientific toolkit, but as an industry where science and technology meet medical needs, market forces, government oversight and ethics.

In addition to scientists, the program attracts lawyers, business professionals and an assortment of others who want to be a part of the growing biotech industry, which generated nearly $60 billion in 2006. Consistently, demand for graduates far outstrips supply.

“No matter where you are in the biotech pipeline, understanding the big picture translates into efficiency, into (consumers getting) faster access to new technology,” says Kurt Zimmerman, director of the biotech master’s program. “Our goal is to help populate all the points along this pipeline with people who have this broad understanding, so that at some point it will become an unobstructed path.”

Along the way, students quickly learn that the biotech industry has a culture and ethic all its own. Things change quickly, and companies face a near-constant onslaught of difficult decisions about which early-stage products to develop and how to fund them. Not surprisingly, the industry tends to attract people who are both pragmatic and idealistic—those willing to acknowledge that companies need to earn profits as they speed potentially life-saving therapies to consumers.

“The thing that really keeps me going is the idea that this work might help people someday,” says Jamie Nehring, a scientist who works in the lab of biochemistry professor Hector DeLuca MS’53 PhD’55, where she is working on an analog of vitamin D that has shown promise as a therapy to prevent diabetes. Although she works in an academic setting, Nehring also sought out the rounded education of the master’s program, which she says has prepared her to follow her project through toward clinical trials and commercialization.

“Now if I do go to a smaller-sized biotech company, I’ll be able to provide input in a variety of areas, not just the science side of things,” she says.

Catch up with…Bryan Renk

THREE YEARS AGO, Bryan Renk was director of licensing at the Wisconsin Alumni Research Foundation when an intriguing new technology hit his desk. Developed in the lab of animal sciences professor Mark Cook, the process derived a powder from eggs that boosted the nutrition of animal feeds. Renk liked the idea so much that he joined the company. He’s now chief executive officer of aOva Technologies, which is selling its feed additive to chicken, hog and fish producers across the country.

You spent a long time working with WARF. How did technology transfer lead to a job transfer?

Well, for me, the first transition was moving from my family’s seed business, which has a long history in Wisconsin and a long history working with the university. So when I went to WARF, I was initially focused on helping WARF work with ag biotech and biotech companies. But later on, as my career there developed, I got to see all these start-ups happening. We were putting the deals together and doing the paperwork, and we could watch the whole evolution. After a while, you start thinking, can I do that? Would it be fun, and would the challenge be there?

I’m sure you saw a lot of different promising technologies. What made aOva the right one for you?

One thing was the professor (co-founder Mark Cook). He had a great track record of commercializing technology, and we thought this had a good chance of success. And it was in agriculture, so my background was a good fit.

Do you think coming from an agricultural background helped prepare you for the uncertainty of running a business?

I think the answer has to be yes. The risk in agriculture is huge. You have to deal with Mother Nature, and you have to come up with solutions in a lot of different situations where there really isn’t an existing answer. Most of the people I’ve known in agriculture are great problem solvers, and they’re solving problems in so many different specialties. You get to cross over a lot, and that’s great training.

Tell me about the name aOva.

Well, the company used to be called Ovatech, but there was some confusion with other existing technologies. So when I came on board, we changed it to aOva Technologies. The small “a” denotes “antibody,” and “Ova” means “egg”—and that’s basically what we do.

You make antibodies in eggs?

Yes. We produce a vaccine that causes hens to produce a particular antibody in their eggs, and then we turn those eggs into a powder that can be used as an ingredient in livestock feed. The antibody works on an enzyme in the immune cascade, which prevents the animal’s immune system from going into overdrive. Basically, we think that animals and humans are overbuilt in terms of their immune response—when it kicks in,it takes away energy from the body and the animal is less efficient in its ability to grow. But this disrupts that function so that the animal can still fight off stresses without using so much energy.

And I imagine that’s appealing to producers.

It is. With feed prices increasing, they’re concerned about feed efficiency, and we think we can help them use less feed to get growth. We also think it can add some health benefits, like helping use minerals better in their diets and reducing phosphorus in excretions.

So you really are a growth business.

We hope so. So far the trend is positive.

Going to Extremes

ON THE ICY BOARDWALK ABOVE BLACK POOL, Tom Schoenfeld is working as fast as his numbing fingers will allow. He lowers a hose into the steaming pool, one of dozens of hot springs in the West Thumb portion of Yellowstone National Park, and then slides the other end into a keg-sized plastic jug. Shuffling along the slick wood planks, he begins piecing together the rest of the water filtration system that he developed for Lucigen Corporation, a Madison-area biotech company where he is vice president of enzyme discovery. The system, which concentrates the bacteria and viruses living within the spring, takes about 30 minutes to set up and an additional two hours to produce a couple of liters of teeming liquid. And though Schoenfeld arrived here at the break of dawn on this freezing September morning, he barely has enough time to get his work done before the tourists arrive. Tourists always delay things.

Researchers who study extremeophiles are partly motivated by curiosity, but also by the realization that extreme forms of life, like high-endurance athletes, have extraordinary abilities.

Despite its name, Black Pool is gemstone blue and perfectly clear. Its scalding waters produce a thick steam that rises from the pool and floats across the boardwalk, enveloping Schoenfeld in a fine mist. Water droplets soak his clothes and frost his eyelashes. As he reaches to switch on the generator that powers his equipment, he hesitates. There’s water all over it-and on the electrical cords leading to the pumps.

“Wear your gloves when you turn that on, man,” says David Mead, Lucigen’s president, who has accompanied Schoenfeld on seven visits to Yellowstone’s hot springs. As much as they can, the two look out for each other in the field and so far so good. Neither has been electrocuted, and they hope to keep it that way.

Electric shock, however, is only one of many perils they face collecting biological samples from Yellowstone’s springs. Once, a herd of unruly bison flushed the researchers from the edge of a backcountry pool, forcing them to wait several hours before they could return to collect Schoenfeld’s equipment. Another time, hiking through a dense forest, Mead tripped and narrowly missed impaling himself on the jagged branch of a downed tree. But above all else, they worry about the hot springs themselves. According to the book Death in Yellowstone, at least 19 people have died after falling or jumping unwittingly into the park’s pools, which are heated by an underground volcano. And as the book relates in sometimes gruesome detail, no matter how quickly a person scrambles out, falling into near-boiling water is a death sentence.

But for Schoenfeld and Mead, these risks are worth taking. That’s because they believe there are million-dollar microbes living in the park’s pools-bugs that, if found and studied, could unlock the doors to major medical breakthroughs and biotechnological advances. And if history is any guide, the bugs are almost certainly there, surviving and thriving in conditions that would kill almost any other form of life.

All Schoenfeld and Mead have to do is find one of them.

Welcome to the adventurous world of extreme microbiology. Like hundreds of other research scientists, Mead and Schoenfeld travel to Yellowstone to seek out extremeophiles-microorganisms that thrive in extremes of temperature and pressure and other inhospitable environments. These bacteria and viruses survive not only in hot springs but in metal-contaminated soils, pools of acid and lakes so salty that crystals bejewel the shoreline. The researchers who seek them out are partly motivated by curiosity, but also by the realization that extreme forms of life, like high-endurance athletes, have some extraordinary abilities. They harbor powerful proteins-known as enzymes-that enable them to make the most of their surroundings, efficiently turning otherwise inaccessible materials into the food and energy needed to sustain life.

“The bottom line,” explains UW-Madison microbial geologist Eric Roden, who teaches an undergraduate course on extremophiles, “is that extremophiles can do things that other organisms can not.”

Scientists first stumbled onto these rare organisms just a half century ago, when microbial ecologist Thomas Brock, then a professor at Indiana University, found a type of bacteria living in Yellowstone’s Mushroom Spring. Brock, now an emeritus professor of bacteriology at UW-Madison, had been searching for an ecosystem hot enough to support only a few forms of life. On a field trip to Yellowstone in 1964, he began examining the spring’s outflow channel. Starting at the cool end of the channel, where a lush, colorful mat of organisms covered the streambed, he worked his way up to hotter and hotter sections.

“When I got up close (to the spring), I started seeing this stuff,” says Brock, who joined the UW-Madison faculty in 1970. “It didn’t have any pigments. It didn’t have any chlorophyll or anything like that, but it looked like it was alive.”

And it was. Brock was able to grow and study this “stuff” in the lab, and in this way discovered the first extremophile, a heat-loving bacterium he named Thermus aquaticus, which is capable of growing at temperatures up to 80 degrees Celsius, not far below the boiling point of water. (Later, it was discovered that T. aquaticus lives in most residential hot water heaters, a harmless squatter.)

Terry Sivesind

While he’s not a bench scientist, Sivesind may have more to do with the growth of Madison’s biotech community than anyone. As a founder of Wisconsin Investment Partners, an angel investors network designed to seed local biotech start-ups, he’s helped raise and distribute more than $5 million to jumpstart fledgling companies. And he’s an industry insider in another way. Since getting in on the ground floor at Promega, one of Madison’s best-established biotech firms, he has been a founder or senior executive at several firms, including PanVera, Mirus, Takara Bio USA, Metabiologics, Renovar, Poseidon Probes and Cellectar. He also runs the Silver Lining Foundation, a private family foundation that focuses on helping Wisconsin’s disadvantaged youth and families.