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.
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.
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.
The first sequencing of the entire human genome was all over the news in 1998, when Michael Sussman, a CALS biochemistry professor, was appointed director of the UW Biotechnology Center. An overwhelming amount of DNA information had become available, and Sussman was poised to help solve the problem of sifting through and interpreting the instructions carried by the genome’s roughly 30,000 genes.
A new tool called the gene chip was critical to that effort. The gene chip is a piece of glass, like a common microscope slide, with hundreds of thousands of different pieces of DNA attached to one surface. It allows scientists to visualize the activity of each and every gene in the genome of living cells instead of having to analyze each gene individually.
When a scientist runs a tumor sample through a chip, for example, it may show that 300 genes have become either less or more active—meaning they are likely to be involved in the cancer process. Indeed, by identifying such activity, gene chips have helped explain why a significant percentage of breast cancers fail to respond to drugs, notes Sussman.
But early gene chip technology was still far from being convenient or flexible. To address its limitations, Sussman sought the help of UW engineering professor Franco Cerrina, an expert in assembling semiconductors, along with CALS bacteriology professor Fred Blattner, who also was an experienced entrepreneur in the field of DNA software. The three went to work on improving gene chip technology—and met with great success.
“The chips we created could simultaneously detect activity in 30,000 genes on a glass surface just two centimeters square, allowing us to measure the entire genetic expression of a newly sequenced organism in a few days at low expense,” says Sussman. “With other chips you would have to wait a month or more and at great cost.”
Their invention in 1999 formed the basis of their company, NimbleGen, which quickly established itself as a maker of high-speed DNA analysis equipment. About five years ago NimbleGen was purchased by pharmaceutical giant Roche for about $270 million
and evolved into Roche NimbleGen, which maintains a development lab in University Research Park. The company continues to develop novel gene analysis and profiling tools that allow scientists worldwide to apply genetic sequence information to advance diagnostics and therapeutics.
While the founding scientists are no longer involved in the company, Sussman continues to innovate new ways to use chips in molecular biology research.
To be forever young—or at least slow down the clock—is one of humankind’s most enduring desires. So it’s no surprise that Richard Weindruch was drawn to study the biology of aging, still a fledgling field when he entered it more than 35 years ago. In particular the idea of restricting calories as a way to slow down aging “jumped out” as a novel and fascinating concept, says Weindruch, a professor of geriatrics with the UW–Madison School of Medicine and Public Health.
The quest to understand and manipulate aging now forms the foundation of a highly competitive industry. And one of the first companies to embark on commercializing the technology needed to identify genes involved in aging was LifeGen Technologies, founded in 2000 by Weindruch and CALS genetics professor Tomas Prolla. Soon after they’d met, their research interests had intersected in what became “an alignment of good luck,” says Weindruch.
His collaboration with Prolla, an expert in gene chip technology, allowed them to fish out specific genes that appeared to control aging in mice that were fed high- versus low-calorie diets. The key to efficiently identifying genes of interest was to look for changes in gene activity or expression. Of the initial 6,347 genes examined on gene chips, approximately 120 showed statistically significant changes in expression. Weindruch lights up when he recounts his excitement at that time. “We were just wired—crazily excited—looking for those genes,” he says.
The two scientists focused on finding “supermarkers of aging,” genes that clearly play critical roles in aging in the context of caloric restriction. That entailed studying multiple strains of lab mice rather than just one and doing massive screens with genetic tools to find shifts in gene expression shared by them all. “We did find very robust gene expression changes with aging in specific tissues,” says Weindruch.
The result: LifeGen has created one of the world’s leading databases of genetic information related to aging. Such data is being used to screen for drugs or nutrients that can mimic the effect of caloric restriction in the body and hence impact aging. “The potential to affect changes in aging is monumental,” Weindruch says.
Late last year LifeGen was purchased for nearly $12 million by Nu Skin Enterprises, based in Provo, Utah. Weindruch and Prolla continue to do research for the company and oversee lab operations that remain in Madison.
Quintessence Biosciences Inc.
Too often RNA is the Rodney Dangerfield of cell biology. As the chemical middleman in the translation of DNA into functional proteins, it generally doesn’t command the same respect as those other two players. But what if manipulating RNA activity could be used to stop the growth of cancer cells?
That’s what CALS biochemistry professors Ron Raines and Laura Kiessling, a husband-and-wife team, set out to do in founding Quintessence Biosciences Inc. nearly a dozen years ago. Their work focuses on modifying a class of proteins called ribonucleases whose job is to break down RNA molecules in the cell. By altering the amino acid sequence of ribonucleases so that they are no longer well controlled by the regulatory protein that usually keeps them in check, the ribonucleases degrade a lot more RNA, disrupting the conversion of genetic information from DNA to RNA to proteins. Quintessence’s most promising product so far, a modified ribonuclease called QBI-139, targets the RNA in cancer cells, thereby killing the cells.
The first phase of a clinical trial testing QBI-139 as an anti-cancer drug—examining its safety and efficacy against solid tumors, including breast, colorectal, ovarian, pancreatic and prostate cancer—is now under way. The trial has enrolled more than 40 patients and is taking place at the UW Carbone Cancer Center and the M.D. Anderson Cancer Center at the University of Texas in Houston. So far patients are tolerating the drug well, with no evidence of toxicity.
Quintessence could be on the brink of something big. But Laura Strong, Quintessence’s president and chief operating officer (and Kiessling’s former grad student), remains cautious, citing a recent study by the Biotechnology Industry Organization reporting that the success rate for bringing new medicines to market—cancer drugs in particular—is as low as one in 10.
“This is not for the faint of heart,” Strong says. “You draw your plans, put them down on paper and develop the milestones, yet it never quite goes the way you envision. Still, it is all incredibly rewarding.”
A lifelong fascination with the egg led Mark Cook, a CALS professor of animal sciences, to create Aova Technologies Inc.
“I’ve always worked in poultry and had always thought that there is really so much more to the egg aside from its use as a food,” says Cook. “Besides, it’s such a cool package. Not only is it sterile, but it contains all that is needed to grow an embryo into a chick.”
Back in the mid-’80s Cook decided to focus one area of his research on a single type of protein that is highly enriched in the egg—antibodies. He had always been interested in how birds transfer their natural antibodies into their eggs, and he pondered how this phenomenon could be applied on a larger scale to benefit the poultry industry.
At the same time, Cook was investigating ways to promote growth in animals through regulating the inflammatory process. He combined these two lines of research, and what resulted was a platform technology involving the manipulation of poultry antibodies to block inflammation, thus improving growth. The strategy entails processing egg antibodies into a powdered food supplement that is then added
to livestock feed. Animals that have experienced improved health and accelerated growth from the feed include chickens, laying hens, pigs, calves, cattle and even fish.
Cook filed patents for his initial discoveries with WARF. He then embarked on years of work developing technology allowing egg antibodies to be produced in a way that was both safe and economical—and which could then be introduced as an additive in animal feed.
Cook now has more than 20 patents to his credit and Aova Technologies has five employees. The company continues to market products worldwide and recently expanded into the $70 billion global aquaculture market.
Despite that global growth, Aova remains in many ways a local company. The animal feed additive is made in Madison, the key ingredient—the eggs—are produced at a farm in Whitewater and the company uses a drying facility in Union Grove. Cook is proud that he has retained these local connections and remains loyal to the state of Wisconsin as his company expands.