Deep Into Bio

Third in a series of articles exploring UW-Madison’s world-class expertise in the life sciences, as a prelude to the BIO2006 Conference in Chicago in April. This piece deals with two high-profile cases of this expertise.

By Katherine Esposito

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Bioscience is blossoming around the globe and at the University of Wisconsin-Madison. In two areas, however — research into human embryonic stem cells and “materials science” — the depth of UW-Madison’s expertise in bioscience is in a class all by itself.

Embryonic stem cells

In 1998, the then-nascent field of stem cell research was catapulted into the public consciousness after developmental biologist James Thomson, working solo in an off-campus lab, announced in the journal Science his successful culture of human embryonic stem cells (hESCs). Although work on mouse ESCs had been performed quietly in many labs for nearly two decades, Thomson’s announcement stunned the world and set the stage for an international race to reap the medical benefits.

Human embryonic stem cells are important because they are so-called “blank slates,” or undifferentiated, capable of becoming any of the 220 types of cells and tissues in the human body. As Thomson proved, proper nurturing of the cells causes them to remain undifferentiated, allowing researchers to probe unknown areas of basic human development. After maturing into more specialized cells, hESCs can serve as windows into the study of specific diseases as well. Eventually, therapies may also result.

Stem cell science quickly became the bio trend du jour, the subject of fierce worldwide competition, intense scrutiny, thrilling announcements and occasional deep disappointment. In 1998 and 1999, Thomson found his earthshaking research the topic of Congressional testimony; the following year, he saw his likeness on the cover of Time Magazine (“one of America’s best in science and medicine,” he was dubbed).

Meanwhile, at UW-Madison, where flash is less common than substance, human ESC science has progressed steadily, aided by Thomson’s calm guidance and increasing support from the Wisconsin Alumni Research Foundation (WARF), the National Science Foundation, private donors and the National Institutes of Health.

Thomson’s latest announcement, reported in Nature Biotechnology only last January, exemplifies the growing influence of UW hESC research. Thomson and his UW collaborator, Tenneille Ludwig, had succeeded in growing two new stem cell lines in the absence of any nonhuman animal products, a vital step toward safe uses for humans. Reported in the wake of a stem cell scandal in Korea, their discoveries sounded a reassuring note. “It is considered a crucial step in stem-cell research because it will allow growth of these cells without using animal products that can harbor viruses and other potential sources of problems,” declared the New York Times.

Today, UW-Madison is well-placed to continue its solid advances in the area of human embryonic stem cell research. After Thomson’s 1998 bombshell article in Science, the university’s support of HES cell research quickly shifted into high gear.

In 1999, the Wisconsin Alumni Research Foundation, the holder of Thomson’s patents, formed the WiCell Research Institute and established Thomson as its first director. WiCell is a private, nonprofit organization established to advance stem cell research. With UW the home of the first federally approved embryonic stem cell lines, WiCell benefited from federal funding to learn more about them. Meanwhile, private, nonfederal funds were provided to investigate other human embryonic stem cell research avenues.

Many UW-Madison faculty members from myriad disciplines, including biomedical engineering, developmental biology, ethics and policy, hematology, chemistry, biochemistry, neuroscience, and cardiac and diabetes research, now work directly or indirectly in the area of human embryonic stem cells; some 40 papers have been published in prestigious journals. Many UW faculty call WiCell a part-time home. WiCell also counts nearly 20 staff members of its own, including scientists engaged in research on basic stem cell biology. Various support staff maintain hESC cultures, distribute them internationally and train researchers in hESC culturing and maintenance.

Meanwhile, external awards to support hESC studies not only maintain the momentum of UW’s research, but confirm its quality.

Early in 2005, Thomson and researchers in other fields received a $1.25 million grant for stem cell research from the W.M. Keck Foundation of Los Angeles. That April saw the establishment of a new stem cell program in regenerative medicine, plus the first NIH-supported interdisciplinary postdoctoral training program in stem cell research.

Later that year, NIH awarded WiCell $16 million to form the new National Stem Cell Bank, to characterize existing stem cell lines and distribute them at lower cost to interested researchers.

Thomson, now in a position to write his own ticket to universities all over, says he prefers the “congeniality” that he finds at UW-Madison.

“It’s a very collaborative, open kind of university,” he says. “There’s very good research here, and [people] tend to help each other when you ask. That openness is not present everywhere.” In 2005, Thomson co-founded a spin-off company, Cellular Dynamics, to investigate the use of embryonic stem cells in the screening of experimental heart medications.

Who are some other path-breaking UW stem cell scientists? They include:

• Jon Odorico, a UW surgeon who is developing cells that secrete functional insulin and that could be transplanted to treat diabetes.
• Su-Chun Zhang, an assistant professor of anatomy and neurology. Zhang and his team have coaxed human embryonic stem cells to become spinal motor neurons, critical nervous system pathways that relay messages from the brain to the rest of the body.
• Ian D. Duncan, a professor of veterinary medicine, now developing cell transplant techniques to repair damaged myelin — the sheathing of nervous system fibers — characteristic of multiple sclerosis. Duncan’s team recently received $3.4 million from the National Multiple Sclerosis Society.
• Clive Svendsen, a UW neuroscientist whose team found a new way to sneak drugs past the blood-brain barrier by engineering and implanting progenitor brain cells derived from stem cells.
• Timothy J. Kamp, a UW heart specialist who has demonstrated that embryonic stem cells can be introduced to damaged heart tissue, develop into heart muscle and into cells that form the heart's blood vessels.

Basic research into embryonic stem cell biology is a critical task, of course, and if UW-Madison accomplished nothing but that, the university could be well pleased. But scientists’ dreams and therapeutic needs don’t end there. That’s where MRSEC and NSEC enter the picture.

Materials Science and Nanotechnology

Well before the National Science Foundation coined the term “nanotechnology,” there was a UW center devoted to it: the “Materials Research Science and Engineering Center (MRSEC) on Nanostructured Materials and Interfaces.” The center, now known simply as MRSEC, was formed in 1996 with a $10.6 million NSF grant and was re-funded in 2000 and 2005. The last grant, for $14.8 million, was an especially big prize.

“These are extremely, extremely competitive grants," said Juan de Pablo, a professor of chemical and biological engineering and the center's director, in a UW press release last year.

More than 30 faculty in 13 UW-Madison departments plus nearly 60 graduate, undergrad and postdoctoral researchers are part of MRSEC. It was one of 11 re-competing nanotechnology centers to receive recent NSF funding.

A related center, the Nanotechnology Science and Engineering Center (NSEC), was formed in 2004 with $13 million from NSF. It involves more than 25 chemists, biologists, physicists and engineers.

Having both centers on one campus is significant, says director Paul Nealey, a professor of chemical and biological engineering. “We’re just one of a couple of universities where that’s happened,” he says.

But it’s in their applications to bioscience where things really get interesting.

Materials science — defined as research in the formation, characterization, and exploitation of materials at the nanoscale, or the scale of individual atoms — touches on nearly every other area of science, bio included.

“We focus on ‘interfaces’: the regions of a system where different entities, materials, liquids, gases, come into contact with one another,” says Paul Peercy, dean of the UW College of Engineering. The interdisciplinary nature of materials science has stimulated many interesting scientific collaborations.

After Thomson’s research was published, it was only natural for materials scientists to inquire after the relationships between nanostructured surfaces and stem cells, Peercy says. The results have been not only gratifying, but path-breaking.

In one particularly fruitful investigation, chemist Laura Kiessling, a 1999 MacArthur Foundation fellowship winner, is seeking synthetic surfaces on which to grow large quantities of hESC, known to be difficult to propagate.

“The cells need to attach to something to grow,” Kiessling says. “The whole idea here is to get a really defined set of conditions so we know all the components and we understand what the signals are.

“It’s interesting in and of itself, because there’s not really simple ways to optimize conditions for cell culture, in general,” she adds. “We’re using it with Jamie [Thomson] for human embryonic stem cells, but you could use it for other kinds of cells as well.”

Other materials scientists are breaking bio-ground in their own ways:

• Nicholas Abbott, UW chemical engineer, who studies the behavior of liquid crystals and their applications to rapid detection of pathogens. Abbott is a co-founder of Madison’s Platypus Technologies, which hopes to commercialize the discovery.
• Franco Cerrina. Electrical engineer Cerrina and others invented a new way to cheaply and simply manufacture the customized “gene” chips to explore DNR. Cerrina co-founded a company, Nimblegen Systems Inc., to produce the chips.
• James Dumesic, a professor of chemical and biological engineering, whose team invented a new way to make a diesel-like liquid fuel from carbohydrates commonly found in plants. Virent Energy Systems Inc., which Dumesic co-founded, is commercializing the discovery.

Editor’s note: The fourth article in this series, in which we ask some of the university’s leading bioscience experts to share their personal vision of where their research may be headed and what the future may hold, will be presented in April. These articles and other related information about UW-Madison’s expertise in bioscience are being gathered in a new bio Web site that will be unveiled in time for BIO2006 in April.

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