Innovation marks UW-Madison contribution to vitamins, drugs, medical supplies

July 6, 2011 By David Tenenbaum

With a long tradition of exploration of medicine and biology, and a research budget that has passed $1 billion, University of Wisconsin–Madison builds on a rich history of discoveries related to drugs and nutrition: Vitamin A and B were discovered here in 1914.

In 1941, Karl Paul Link discovered dicumarol, an anti-coagulant and poison. From dicumarol, Link synthesized coumadin (Warfarin), the first widely effective rat poison. Coumadin, the first safe medical anticoagulant, is still widely prescribed.

Ever since biochemist Harry Steenbock discovered how to enrich the vitamin D content of foods through irradiation in 1923, the vitamin and its many derivatives have been a mainstay of UW–Madison pharmaceutical research. Facing considerable commercial interest in the vitamin, Steenbock believed the university should benefit, and together with Dean Slichter, he founded the Wisconsin Alumni Research Foundation (WARF), which opened in 1925 as the nation’s first university technology transfer office.

The independent, non-profit WARF remains one of the most successful university technology offices: by now it has patented 1,900 university inventions and contributed $1.07 billion to university research, programs and initiatives. In harmony with its origin, WARF’s largest source of revenue has been the many vitamin D inventions by biochemistry professor Hector DeLuca. Long after vitamin D supplements (primarily in milk) eliminated the bone disease rickets, the vitamin is being used to combat osteoporosis, kidney disease and other diseases.

These advances, and many others, are part of the reason why UW–Madison has a $12.4 billion annual impact on Wisconsin’s economy that helps support 128,146 jobs across the state.

Beyond vitamin D, the university faculty and staff have discovered many drugs and related products that have benefited Wisconsin businesses large and small.

As surgeons began moving organs to deathly ill patients in the 1980s, the lifesaving potential of transplants for kidney, liver and heart disease depended on keeping organs alive during removal, transport and surgery. The invention of a solution with the ideal chemistry for sustaining organs by UW–Madison transplant surgeon Folkert Belzer “revolutionized transplantation by extending the lifespan of organs outside the body to 18 hours and beyond,” says John Bruens, chief commercial officer at Bridge to Life, Ltd.

Belzer’s UW Cold Storage Solution quickly became the standard method of storing organs, and so in 2005, when Bridge to Life was formed to commercialize another organ-preservation innovation, the company licensed the trademark from WARF.

“Ours is an exact duplicate of Belzer’s original formulation, though we have made some very important improvements which avoid the need for refrigeration during manufacturing, shipping and warehousing,” says Bruens.

The company contracts for production with Preservation Solutions, Inc. of Elkhorn, Wis., and is developing an experimental method to “feed” stored organs with ATP, the energy molecule of life.

The only proven way to slow aging in yeast, rodents and non-human primates is to reduce calories, while still eating all necessary nutrients. “Caloric restriction” is an area of intense interest at UW–Madison, where some of the most compelling proof for the concept comes from monkeys that have eaten a reduced-calorie diet for more than 20 years.

Richard Weindruch, a professor of geriatrics at the School of Medicine and Public Health and the principal investigator of that monkey study, and Tomas Prolla, a professor of genetics, co-founded the spinoff LifeGen, which is exploring how to obtain the benefits of caloric restriction without cutting out 30 percent of the calories.

The goal is to find out exactly how caloric restriction slows aging, says Prolla. “Starting about 10 years ago, we discovered how to use patterns of gene expression to measure the aging process, and to tell us whether a compound can mimic the effects of caloric restriction.” Prolla and Weindruch have identified a set of genes that shows the overall speed of aging. “We can use these ‘supermarkers of aging’ to discover compounds that either retard aging, or mimic effects of caloric restriction,” Prolla says.

As it explores formulations that can oppose aging, LifeGen has partnerships with Purina, the animal-food giant, and Nu Skin, a maker of nutritional supplements. The company has about half a dozen employees, Prolla says. “Most have a Ph.D., which you need for this type of work.”

A spinoff called Coating Place, Inc., concentrates on coating the active ingredient to improve the performance of a drug’s active ingredient. The basic “fluid bed” technique, invented by Dale Wurster, a professor of pharmacy, spray-applies a coating to a powder suspended on a bed of air, says Timothy Breunig, CEO and president. “This can give a time release, an enteric coating so the product is not released in the stomach, anything you want to modify the release characteristics of an active pharmaceutical ingredient.”

Coating Place, founded in 1976 and headquartered in Verona, serves the pharmaceutical industry.

“They deliver a white granular powder, and take away a white granular powder that has different properties,” says Breunig. “We have 130 employees and over $20 million in sales. About 50 percent of our employees have bachelor degrees, and more than 50 were educated at a University of Wisconsin campus.”

Drugs that fight Alzheimer’s disease are on anybody’s priority list, says Trevor Twose, chief executive officer of Mithridion, Inc. in Madison. The firm started in 2006 by licensing a discovery from Jeffrey Johnson, a professor of pharmacy, who had found a small molecule that seemed to defend against the plaques that kill neurons in Alzheimer’s. Within 20 months, the company had developed five candidate drugs, but the original invention did not pan out, says Twose.

Mithridion is engaged in clinical trials of one compound that affects response to the neurotransmitter acetylcholine, and has “two other drug candidates invented by our people in Wisconsin.” No matter which compound succeeds, he says, “We were founded in Madison to take advantage of an invention at UW–Madison. WARF is an investor, and most of our people are graduates of UW–Madison. If we succeed, the entire state will benefit.”

It’s a medical device rather than a drug, but the silver-impregnated dressing invented by Nicholas Abbott, a professor of chemical and biological engineering, and being commercialized by ImBed Biosciences, has exciting potential for controlling wound infections, preserving the benefits of antibiotics, and hastening healing.

According to Ankit Agarwal, co-inventor and a post-doctoral fellow in engineering who is ImBed’s CEO, “Silver is used in some dressings because it has bactericidal properties, but high loadings of silver also can slow healing. Our tests in animals show that when we imbed nanometer-size particles of silver into a biologic dressing, we reduce wound infection, promote faster healing and circumvent frequent painful dressing changes.”

With support from several campus researchers, ImBed is moving toward an FDA application for an investigational device.

In the story of technology transfer from American universities, biochemistry professor Hector DeLuca is a link to a glorious past. After all, his advisor, Harry Steenbock, had worked with E.V. McCollum, discover of vitamin A, before discovering how to produce vitamin D with ultraviolet radiation. Vitamin D has become DeLuca’s life work, and the source of several successful spinoffs.

Two DeLuca firms have been sold. Bone Care International, a maker of drugs to treat dialysis patients, was sold in 2005 to the biotech firm Genzyme for about $600 million, and Tetrionics was sold to Sigma Aldrich Fine Chemicals.

DeLuca’s next bet, Deltanoid, is testing several vitamin-D derivatives against psoriasis, osteoporosis, and kidney and autoimmune diseases. In clinical trials, one derivative, “seems to be very effective for stimulating bone growth,” DeLuca says. Other Deltanoid products are approaching the human testing phase. “Our idea is to take raw university inventions and develop them to the point where they can be licensed at a good rate to industry, and then turn around and develop something else,” says DeLuca.

Vitamin D, as DeLuca acknowledges, is the current “human health darling,” with a wide range of claimed benefits, but despite having devoted his life to the vitamin, DeLuca is a bit skeptical.

“People have correlated the blood level of vitamin D with health benefits, but these are not necessarily related as cause and effect, although the vitamin and related compounds are clearly related to osteoporosis and some types of kidney failure,” he says.

“Wisconsin is a strong university when it comes to scientific matters,” says DeLuca. “It ranks among the best, and lots of great ideas come out of this place. When they are put into practice, they can really build the state economy.”

UW-Madison, DeLuca says, “lives on the good will of the people in the state. We are here because of the state of Wisconsin, and its people. Starting a business is not a bed of roses, but if you are really interested in getting your invention out to the public so it benefits people, a business is the way to go.”

Even for a professor with an enviable record of inventions, however, a spinoff business “goes a lot slower than you think it should go,” DeLuca says. “You have to be able to pull yourself up by your own bootstraps, raise the money and get the leadership you need, but these spinoffs get started because the people of this state believe in this university. It has delivered, and we think it can keep delivering.”