The Brave New World of Steve Stice

B Y - D E B O R A H - B L U M - ( A B J '7 6)

Cloning expert Steve Stice has opened a biotech company on campus. His goal is to genetically alter "pharm" animals to produce new drugs for humans—and UGA will own the patents.

Here's what's on display in Steve Stice's office: There's a sunlit photo of his family on a fishing expedition—and the resulting glossy tuna mounted on the wall. There's a fantasy baseball league trophy, inscribed "Purple People Eating Pigs," perched high on a shelf. There are the pale, carved jade animals, a gift from his father, that are meant to represent the world of cloning possibilities, from the realistic (a mouse) to the wildly improbable (a snarling tiger).

Here's what's not on display: the trappings of scientific celebrity. At age 39, Stice—one of UGA's newest Eminent Scholars—has already made international headlines as a pioneer in the super-hot field of animal cloning. But Stice keeps his press clippings tucked away in a cabinet and he hefts them out—we're talking two fat, heavy binders here, compiled by a media clip service—only on demand. "It's a matter of priority," he says.

Stice and his professor genetically altered the fetal cells of cows, then cloned those cells and raised the offspring. The first two calves, George and Charley (above, far left), are from the same cell line as the other four—but older.

Stice has been making news since he was in graduate school. While still working on his Ph.D. in 1988, he did one of the first successful demonstrations of cloning techniques in rabbits. Then, barely 10 years later, in January 1998, he and his senior professor at the University of Massachusetts announced that they had gone beyond cloning. The team of Robl and Stice had broken through a long-standing barrier in biotechnology. They'd genetically altered the fetal cells of cows, then they'd cloned those bioengineered cells, and they'd raised the clones. It was a rare and genuine first. George and Charlie—little black and white Holsteins with long eyelashes and bashful behavior—were born into a media blitz, with much use of the apparently irresistible headline, "Brave Moo World."

"We announced it at a meeting about a week after their birth," says Stice. "It was,"—he draws a slow breath—"very intense."

George, Charlie, Stice, and Robl were finally, and with some relief, upstaged by the Monica Lewinsky saga (they were bumped off "Face the Nation" for new scandal news). But Stice's work has become even more ambitious, and the media has not forgotten. The Wall Street Journal chronicled his move from Massachusetts to Georgia last year, noting that Stice was one of the few scientists who might live up to the promise of creating superanimals, ranging from more productive farm animals to "pharm" animals, genetically altered to produce drugs. Since arriving at UGA, Stice has been called by The New York Times, U.S. News & World Report, and Newsweek.

Stice remains unimpressed—and slightly amused—by the media-darling phenomenon. What's his favorite story from the limelight? He grins. Stice is an athletically built man, with short dark hair, dark-blue eyes, and a smile just a watt or two short of pure mischief. "We were on the 'CBS Evening News,' " he recalls. "And while we were getting ready, the producer came by to tell us that we were going to be the first story because," and he pauses for the punch, "Dan Rather just loves this s___."

He's still laughing as he tucks the binders neatly away.

Stice's position is a balancing act between industry and academics. His appointment involves 51 percent time as a UGA professor and 49 percent as an officer of a fledgling biotechnology company called ProLinia.

Wasn't our timing perfect?" Clifton Baile is also smiling. Baile is both an Eminent Scholar in agricultural biotechnology and a special assistant to UGA's vice president for research, Joe Key. Baile has gray hair, a firm handshake, a direct gaze and a grin with just as much mischief as Stice's. At the moment, he's cheerfully congratulating himself and the University for luring Stice to Georgia in the teeth of stiff competition: "He made the news at just the right time and he's such a nice guy. He can take on the most adversarial question and be reasonable. He's an exciting scientist. He could have gone anywhere."

Endangered today, but reinvented tomorrow?

Meow!Amidst his research to clone more animals for medicinal purposes and hunger prevention, Steve Stice and his wife Tracey have founded Safe Harbor Foundation, Inc.—a non-profit organization devoted to preserving endangered animals' genetic diversity.

"As an endangered species' habitat shrinks—largely due to man—populations become isolated and genetic diversity decreases as a result of inbreeding," says Stice. "Safe Harbor hopes to work with zoos, animal parks, and other institutions to freeze and store the tissue of endangered species."

The idea, says Stice, is to save that genetic material until the advent of new technology—and, God forbid, the extinction of a species—makes it both possible and necessary to regenerate the species. The process begins with a small skin biopsy taken from the endangered animal. The sample is sent overnight to UGA, where Stice and his technicians take over. They grow the cells to sufficient quantities, then freeze them until universal cloning is developed—a procedure still in the theoretical stage.

"This will be an additional method to the already existent method of freezing animals' sperm and eggs," says Stice. "The difference is that the viability of sperm and eggs are difficult to maintain after thawing. Our samples have an 80 to 90 percent viability after thawing."

Stice envisions the project being funded entirely through private investors. "This is a simple way that people can help preserve the animal species," says Stice. "Everyone has a role in the stewardship of the world and its inhabitants."

Attacking Parkinson's Disease at the molecular level

The rat is used for Parkinson's experimentation. Top: Left side is healthy rat brain (red). Right side is deficient in nerve cells that prevent Parkinson's disease (pink). Bottom: Left side is healthy. Right side has transplanted cloned cattle nerve cells (red), partially restoring cell deficiency in Parkinson's.
In an attempt to combat Parkinson's disease, Stice and a team of scientists from all over the U.S. are collaborating under the biotech umbrella, CytoGenesis, Inc. (CGI). The goal is to both develop cell therapy using neural stem cells to replace those lost during Parkinson's disease and to deliver the cells to the brain. Transplanted cell survival is now about five percent; Stice's goal is to increase survival to 40 percent.

"Our chances of success are good," says Stice. "Parkinson's is a complex disease, but we have a lot of good people working on the problem." Included in the group is Brian Condie, a researcher at the Medical College of Georgia who has worked with neural stem cells for years. The collaboration is part of a new UGA-MCG biomedical initiative.

"Research is becoming more and more interdisciplinary and complicated," says Condie. "In order to pursue different major projects, such as Parkinson's research, you have to put together teams with many different types of expertise."

"The home run will be if our work leads to a cure," says Stice. "But there is an immense amount of work that needs to done before that happens."

Alex Crevar

But Baile was determined: "When it was apparent Steve was interested in doing something different, I took it on myself to get money to bring him here and to use up all his vacation time until he said yes." Baile, former director of research and development for Monsanto's animal sciences division, had been an admirer of Stice's work for years. There was something else as well; the University is interested in researchers who want to push the envelope. "It's so much easier to dream," says Baile, "with people who want to dream."

Key recruited Baile to pioneer a modern academic yet applied research program. "It's Joe Key who really makes what we want to do possible," Baile insists. Baile, who joined the UGA faculty in 1995, straight from Monsanto, is a man with a vision. Call it two visions really. First, he wants to help create a new model, a comfortable balance between research and industry in an academic setting. And second, he hopes to put UGA out front in those emerging disciplines—plant and animal cloning, for instance—which should thrive in that heady mix of pragmatic investment and academic exploration.

"What we're trying to do is build on frontier areas," says Baile. "There are real opportunities in several areas of plant and animal science. It's those niches that interest me. I want to build full credibility there. And remember, there's only so many of those opportunities out there. You've got to be riding a crest to make that happen. We don't in any way replace the fundamentals of a university; I hope we complement it."

Working in Stice's laboratory gives student workers like Marie Esposito, a master's candidate in animal science, a revealing, first-hand look at cutting-edge biotechnology.

To make that plan work, UGA added more than just Stice to its already impressive animal genetics faculty. There's also renowned plant geneticist, Andy Paterson. And there are plans for more such ambitious hires. A primary recruitment tool is the mixture of academic setting and start-up companies.

Stice's position embodies the industry-academic balancing act UGA is attempting to create. His appointment involves 51 percent time as a professor; 49 percent time as an officer of a fledgling biotechnology company called ProLinia, which will focus on the use of cloning and transgenic techniques to improve livestock. His office is in the Dairy and Animal Science Complex; so is his ProLinia office. The University shares his salary—$140,000 a year—with the start-up company. ProLinia, although mostly just a company on paper, has attracted investors as far away as California.

"An essential component of these start-up companies is having a technology champion," says George Murphy of Menlo Park, a specialist in new venture development who is among the founders of both ProLinia and AviGenics, another start-up company based at UGA. "Someone like Steve is absolutely essential, and what's unique about Georgia is that he has both an academic appointment and the freedom to participate in a new venture."

"It's an ideal situation for an entrepreneur professor," says Stice, whose formal title is Georgia Research Alliance (GRA) Eminent Scholar in Animal Reproductive Biology. The title includes one other vital aspect. GRA is crucial. The alliance is a coalition formed by the state's research universities, government and industry, specifically to apply research, to make it easier for industry to really use a promising scientific discovery.

GRA endows its Eminent Scholar chairs—Baile is also a recipient—so that researchers can move rapidly in getting their research going. Stice's chair has a $1.5 million endowment, which goes toward salary, equipment, and support of graduate students and post-doctoral hires. He has already purchased some of the machinery—powerful microscopes and precision-balanced operating arms—used in transferring genetic material from one cell to another. They cost $70,000 each; so far, he's assembled three. The harder part, he says, is training people to work with them. "You have to be the kind of person who will spend a whole day doing tedious and frustrating work that sometimes fails anyway," he says. "And then you have to be able to come back and do it again."

Despite the industrial interest in Stice's work, all of this time, labor, and equipment is by no means a giveaway by the University—in fact, the opposite. The patent on any and all of Stice's discoveries, on either University or ProLinia time, will be held by UGA. Says Vice President Key: "The process will work, I am certain, if we have the right people doing this. And Steve is one of the most straightforward, honest, and ethical people I have ever met. We think that we have a very good model here—and a very good person."

You might consider Stice's childhood as the ideal upbringing for a future entrepreneurial professor. His father was a patent attorney with an affection for agriculture. When Stice was in eighth grade, his family moved from Minneapolis to a 500-acre farm in central Illinois. Stice considered becoming a vet, but it was the science behind the animals that interested him. When he started at the University of Illinois, he got involved in an experiment to create a hybrid goat-sheep.

"I loved that—researching a question, trying to find the answer, learning about embryos, how to alter them. I was just fascinated," he recalls. "I still consider myself a developmental biologist, first of all." He graduated from Illinois with a B.S. in agricultural science in 1983 and received an M.S. in animal science from Iowa State two years later. But the years in school, immersed in basic research, had made him uncertain of his future. He loved the science but he'd grown up believing that work should produce—be used, be useful.

He took a year off and went back to basics. He developed a ventilation system for pig barns. "My father was interested in new product development; my brother has a successful biomedical company," he says. "The year off gave me time to think about what I wanted to do."

When the ventilation project was done, he enrolled in the animal science program at the University of Massachusetts in Amherst, receiving his Ph.D. in 1989. His major professor there was James Robl, already a pioneer in animal cloning techniques. Stice impressed Robl as a scientist, but more than that, as a disciplined and decent person.

"Steve did an outstanding job on his Ph.D. under very difficult conditions," says Robl. "Soon after starting his program, he learned that his wife, Tracey, was pregnant with twins, and at the time he had one daughter who was only about a year old. The twins were born during the middle of his Ph.D., which, along with the stress of having three children in diapers, created a financial strain as well. Steve located, on his own, a start-up biotechnology company and worked out a situation where he could work part-time for the company and complete his degree at the same time."

Mixing business with education

Steve Stice's appointment to UGA is only 51 percent academic, but the intellectual momentum he generates is ultra-valuable to the students he comes in contact with both inside and outside his lab. Case in point: Stice recently spoke to a class of animal science majors, dispensing key insights about the differences between vet school and graduate school.

"Whatever you do, don't do it for the money because only a rare few are paid accordingly," Stice said.

From the back of the room, Geary Bush asked, "I want to be involved in breeding pigs, but I'm not all that excited about taking calculus. What road should I take?"

Stice looked at the ceiling for a moment, searching for the correct response, then laughed softly—not to mock the freshman from Donaldsville but to put the room at ease. "Well, I don't think you are going to get out of it quite that easy," he said, "but I can give you the name of a few pig improvement companies that would be a good place to start interning."

Stice gives about 10 lectures a semester. He doesn't actually teach classes, but he does serve as the major professor for one very lucky animal science graduate student per year—a number that will rise to two or three in subsequent years. He also makes his research and his laboratory available to two undergraduates every summer—who may elect to remain on-board as lab techs.

"We provide a way for students to learn and to see how a small business runs," Stice says of his part-corporate and part-academic relationship with UGA. "Sometimes just giving students the opportunity to find out if lab is or is not the place for them is education enough. I recently had a student change his field from reproductive physiology to business."

Tonya Garner worked for Stice as a summer undergraduate. She incubated and enucleated cow eggs as they came into the lab.

"I searched out Steve to work in his lab and learn about the work he was doing," says the senior from Duluth. "His guidance and the things I learned about cloning and molecular biology will help me make a better decision about how I want to apply myself in horse medicine or horse reproduction. I would have never come to such conclusions without someone of his caliber on campus. I was able to do cloning work hands-on instead of having my nose buried in a book."

Cattle cloning scientist John Gibbons, a member of Stice's research team, believes the notoriety Stice brings to a university is immeasurable. "When great research has a seamless relationship with a university, other great minds take notice" says Gibbons. "This is a great educational tool for an institution."

Stice believes the energy students bring to any research project has enriched his decision to relocate to Athens and UGA.

"After spending five years in a large Fortune 50 company, it's nice to be with people who do the research for the sake of the research," he says. "Students' youth and vigor keep research lively, and I wouldn't want to be in any other place but a university setting."

Alex Crevar

Stice puts it this way: "Having three small children is a great incentive to finish your degree. It pushes you very nicely." He credits his wife and her mother, who came to help keep house when the twins were imminent, with keeping the family going.

Nevertheless, as Robl points out, Stice did finish his degree in less than three years—and his dissertation was groundbreaking. He found the natural activation signal in sperm cells that give the egg the jump-start to start dividing after fertilization. The signal was a very specific soluble protein, and since Stice's dissertation a number of labs are trying to purify it for use in cloning, fertility treatments in both humans and animals, and contraception. The protein may also be valuable in understanding accelerated cell division in cancer. "At the time, it was very controversial," says Robl. "But now it's one of the most referenced studies in the field."

Stice left Massachusetts after graduation to take a job with American Breeders Service, a Wisconsin company focused on improving animals through biotechnology, but Robl wanted him back. "I worked very hard to get him to come back," he says, and after five years with ABS Stice returned to Amherst. He and Robl co-founded a small biotech company called Advanced Cell Technology. He also was named an adjunct professor at U-Mass. The two scientists then began the ambitious project to create George and Charlie. Their goal was both simple (proving that it could be done) and complex (actually doing it.)

Previously, the two techniques—cloning and bioengineering—had operated separately. Stice and Robl wanted to merge them. First, they wanted to alter the genes in a fetal cell. Then they wanted to clone those cells, and duplicate them into matched embryos. Then they wanted to raise the embryos into healthy animals—perhaps the most difficult challenge of all. The survival failure rate in cloned embryos—more than 80 percent—is one of the biggest obstacles in the field. "It's a black box," says Stice. "We're all still trying to understand it and overcome it."

Robl and Stice knew that, if successful, they would have demonstrated an enormous potential for using animals in pharmaceutical production. For instance, one might induce the production of human serum albumin—a vital blood protein that regulates fluid levels—in cattle. Albumin is essential in countering lethal dehydration. It's used to treat people suffering from liver disease or from severe burns or malnutrition. Worldwide, about 400 metric tons of albumin are used every year for medical treatments. The source is donated blood products. Stice estimates that one bioengineered cow could produce 176 pounds a year, released into the milk. In one scenario, the cows would simply produce insulin-rich milk. "A lot of people asked us how our little males, George and Charlie, were going to do that," Stice says. "But, of course, that wasn't the point. What we did with them was introduce a marker gene. We wanted to demonstrate the principle."

In the end, though, proving the principle still turned out to be easier than applying the work. There are still no plans for albumin-rich herds. For Stice, with his desire to see his research make things happen, the slow, cautious pace of pharmaceutical work was increasingly frustrating. Baile, who had been with Monsanto through some tough public battles over genetically engineered products, sympathized instantly. He suggested to Stice that he come to UGA and try a fast-moving line of research focused on improving farm animals, staying clear—at least for now—of the regulatory barriers that surround potential human applications.

"That doesn't mean I'm a critic of the FDA," says Baile. "They're the best in the world. It's vital that people have confidence in what we are doing. We're focusing on agriculture because right now we can license stuff that we couldn't if it was for human use. That doesn't mean that the human implications aren't important—they still drive the field." Stice hopes his discoveries with farm animals will be useful in treating human diseases. But he liked the idea of first focusing directly on agriculture.

Robl says he recognized that Stice needed to create his own projects. "Absolutely, I didn't want him to leave. And, absolutely, I think he will be great for Georgia. One of the most rewarding things I do is to train students and then see them go off on their own and be successful. Steve's success at UGA will, in part, be my success."

As Michael Cassidy, vice president of the Georgia Research Alliance tells it, they connected Steve Stice and success almost instantly. Stice had done some consulting for the state in 1995, when the GRA was recruiting a poultry research business. "Right away, we thought what a catch he would be for our state," says Cassidy.

Cassidy shares Baile's vision of making Georgia an international center for applied agricultural research. Sure, he says, there are schools like Stanford or MIT that slowly and deliberately build reputations as leaders in the field. But there are other places—and UGA is one of them—which want to deliberately speed the process. "Why let it take 20 years, 40 years?" says Cassidy. "Georgia is one of a handful of states being very aggressive about this, and the centerpiece of our strategy is building a brain trust. We want to build for the future a technology driven economy.

"Steve's a different breed, but so are a lot of the others we've endowed—about 30 chairs so far. By and large, these folks are all wired differently than what we think of as scholars. They are all academically strong, but in addition they are interested in the entrepreneurial side. That makes them—at least we hope—change agents."

Alta Charo, a member of President Clinton's National Bioethics Advisory Commission, says some uncertainty still exists over whether such methods actually drive research forward. Charo, who holds joint appointments in law and medicine at the University of Wisconsin-Madison, says, "There's a very lively debate over whether, in the end, an influx of collaboration has sped up development of the field because of enormous infusion of cash, or slowed it down because of more limited information diffusion."

So far, she adds, no one has adequately answered that question. "You'd have to say the jury is still out," she says. Key agrees with that assessment. But he also hopes the University will achieve a successful balance of interests. UGA requires full disclosure to deans, department heads, and administrators of any proposed start-up venture. Stice's contract also insists that information be shared. Even if a patent is pending, the University retains the right to demand publication by the end of three months. "That's more than fair and I would hope we could publish faster," says Stice. "There's no reason you can't turn a patent around in a few weeks." (He should know—U-Mass holds eight patents based on his work and Advanced Cell Technology holds 10.)

"The University has a policy which deals with both conflict of interest and conflict of time," says Key, "so scientists know up front what is expected on both counts regarding outside activities—including work with start-up companies. Grad students, and the right to publication are carefully and fully protected."

At the same time, some corporate experience unrelated to the dissertation research can be very valuable to students and/or postdocs, he adds. Stice also believes that a balance of pure academic and industry research is valuable for young scientists when they move into the job market.

"We believe this is an exciting program," says Key, but he stresses that UGA also believes it will thrive only in a climate of openness: "This will work best if everyone is told everything."

Stice's research might make it possible to produce bio-engineered cows with milk rich in, say, albumin, which is used to treat people suffering from liver disease, severe burns, or malnutrition.

Of course, at this point, Stice doesn't have that much to tell. He and his wife and the three children—Danielle, 13, twins Phillip and Claire, 11—are officially and fully moved, leaving behind eight hilly acres in Massachusetts and settling into a new home in Clarke County. "My wife said she wanted a brand-new house with a short driveway." says Stice. "The other driveway was an eighth of a mile and steep, so you can imagine it in the winter." The new property does have room, of course, for a dog, a cat, and a rabbit. "The kids have adjusted really well; we've felt really welcome here."

It's fair to say, though, that if the family is still adjusting to their new home, Stice is still adjusting to his new facilities. They are also brand new: labs with smooth black counters and pale wood cabinets, cattle and pig holding facilities bright with new metal and smooth plastic. His staff of four—comprised of a visiting scientist, a postdoc, and two graduate students—see sidebar—is also new, but beginning to settle into a nice rhythm.

Stice is working with a small herd of cattle not too far from Athens and—as Baile predicted—he envisions a great future at UGA. He wants to take on that big hurdle in cloning, getting the survival rate up. He wants to explore the best directions for improving cattle and pigs, be it greater muscle mass or longer legs. At least partly, his vision is to tailor the animals to the hopes of the farmers.

Does that give him, or researchers like him, too much power over the shape of life? Stice believes researchers need to tread this path with caution and with respect. "I disagree with scientists who say just that society should decide," he says. "As scientists, we have to think about the implications." He points out that there are natural limits to any manipulation: "We're not going to be making two-headed cows or three-uddered goats. It's always what Mother Nature allows."

He says that even small start-up companies are moving toward having ethical advisory boards. "And I think that's good," he says. "It's good to have that kind of feedback." Animal rights activists, in particular, object to cloning cows and pigs, but there has been no hostile reaction to Stice's appointment. Baile credits that to Stice's straightforward decency in discussing the issues. Charo, of the National Bioethics Advisory Commission, says two kinds of research tend to provoke public criticism: human applications and cross-species development.

So far, Stice plans no such lightning-rod kind of work. It's the basics that interest him now. If his work does excite coverage, well, "I think these are topics that need to be discussed," he says. There are undoubtedly press clippings to come. And also, undoubtedly, they will be tucked tidily away, taking last place in priority behind the family photos and the stuffed fish.

Pulitzer Prize winning science writer Deborah Blum (ABJ '76) is a journalism professor at the University of Wisconsin.

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