The rhinestone glitz of Nashville's Music Row is not far from the Vanderbilt University Medical Center laboratories of Carl Hellerqvist, or from the suburban business office of his biotechnology firm CarboMed. Like country music in the last couple of decades, Hellerqvist's job description has gone more "mainstream," coming a long way from the days when graduate students attended his lectures about the arcane sugars used by microbes to build their cell walls. Vanderbilt itself has been slower to evolve, and is only now attempting to reap the royalty benefits from the corporate collaborations that are the norm for universities in other parts of the nation.

Vanderbilt is ranked 14th in the nation academically and 61st in royalty income, "and it would be 220th if not for Hellerqvist," Hellerqvist says in a laconic, slightly Swedish-tinged tone, indulging a fondness for referring to himself in the third person. Biotechnology entrepreneurship began at Vanderbilt in 1990 when Hellerqvist founded CarboMed to develop what is now known as CM101, a molecule derived from a bacterial sugar. At CarboMed, Hellerqvist has demonstrated CM101's potential to treat cancer, soothe rheumatoid arthritis, curb wound healing that has run amok, and even to allow paraplegics to regain some use of their limbs.

It is perhaps surprising that a structural biochemist specializing in bacterial carbohydrates would come up with an agent that has allowed paralyzed mice to walk again. The research with CM101 developed precisely due to the fact that Hellerqvist came from Sweden. When he arrived in Nashville in the 1970s, Vanderbilt's medical staff included a physician-researcher, Mildred Stahlman, who specialized in premature infants. Stahlman, honored today by neonatologists as a founder of the discipline, had been hosting a steady stream of young physicians-in-training from Sweden (she had done postgraduate work at the Royal Caroline Institute of Medicine in Stockholm). The Swedish trainees came to know their fellow countryman Hellerqvist during their stints with Stahlman. In 1978, Stahlman received a center grant to investigate the modus operandi of a bacterium that specifically infects newborns - it appears to be innocuous to older humans - and Hellerqvist knew a lot about bacterial biochemistry. The visiting Swedes brought the two researchers together.

Hellerqvist's methods allow one to derive the complete structure of a bacterial polysaccharide from a few milligrams of material, a task that used to require a hundredfold more. His work also allows the virulence of a pathogen to be correlated with the carbohydrate structure of its cell wall. Hellerqvist isolated the CM101 polysaccharide from a baby who had been suffering from a group B streptococcal lung infection, but had recovered. When they tested CM101 in mice, which for a short time surrounding birth are susceptible to the same infection, Vanderbilt researchers discovered a cell surface receptor expressed in the blood vessels of the newborn lung, the last vasculature to form in a baby. This receptor is the site where the group B strep bacterial poison attaches, commencing an attack mediated by an alerted immune system.

The finding led Hellerqvist's team to the idea that pathological vasculature - new blood vessels that form in response to loss of oxygen - is similar to embryonic blood vessels and contains primordial metabolic markers, such as the receptor that happens to recognize a bacterial mimic, CM101. The demands of tumors for an ever-expanding blood supply, the injury to starving heart muscle after coronary clots, and the inflammatory response that runs out of control in rheumatoid arthritis all have the hallmark of pathological vasculature that has reverted to the embryological state. CM101 will "tag any vessels that want to sprout," Hellerqvist says. "I tested the ability for CM101 to bind to tumor vasculature in human tumors - bingo! Tumors in mice were ablated by CM101 infusions, which induced the same inflammatory destruction seen in the newborn baby lung." He further notes, "We discovered that CM101 inhibited scarring in the mouse model [and] retroactively could conclude from the clinical trial for cancer that. . . patients' ulcers healed and that Kaposi's sarcoma lesions were no longer detectable."

Another accidental meeting of specialists provided the link with nerve injury and recovery. Hellerqvist happened to sign on a Polish emigre, pediatrics research physician Barbara Wamil, whose husband was on the anesthesiology faculty doing research in electrophysiology. Artur Wamil tested CM101 in his nerve cell assay, and it turned out to provide a neuroprotective effect.

Hellerqvist assigned the CM101 patent to Vanderbilt, which granted CarboMed a world-wide exclusive license. The company's genesis was not without pitfalls, as all of the parties involved were new to business. For example, the then-vice chancellor of the medical school voiced concern over conflict of interest, pointing out that if Hellerqvist were to be CarboMed's president, he would in effect be granting himself his own research funds. The rather unusual compromise reached was that Hellerqvist filled the slot by appointing his own wife (who was adept at the corporate legalities that her husband admits he prefers to delegate). "Those were very early days," says Vanderbilt technology-transfer director Larry Steranka. "CarboMed now has a CEO. It is not Carl's wife."

CM101 has completed two Phase I tests in cancer patients; its progress has allowed tiny CarboMed to enter a licensing agreement with a big biotech player, Zeneca Ltd. (now part of AstraZeneca). Vanderbilt has somewhat belatedly begun developing more corporate connections under its new vice chancellor, Harry Jacobson, a nephrologist with experience in business ventures. Steranka is presiding over the drive to involve the university's faculty in entrepreneurship, which is fueled by a recent infusion of $10 million from the university endowment. There are currently eight companies founded on research by Vanderbilt faculty - the professors assigned their work to Vanderbilt by policy, and the university in turn licensed the work to the companies. All this activity earned the university $1 million in royalties in fiscal 1998. At the end of that year, CarboMed hired John G. Watson, a former executive with several pharmaceutical houses, as president and CEO.

Hellerqvist has made wise use of serendipity and personal contacts, in both his research work and business affairs. Hellerqvist wanted to control the route taken by his corporate start-up - as it happened, he had consulted on the scientific advisory board of a biotech company, GlycoMed, which was the self-proclaimed specialist in carbohydrate drug candidates. In the early 1990s, the start of biotech's heyday, when other companies were touting peptide agents, GlycoMed hawked carbohydrates to venture capitalists. But GlycoMed's carbohydrates were shelved during a buyout by competitor Ligand, which wanted only some of GlycoMed's products. In fact, GlycoMed had sought to acquire CM101 for the GlycoMed pipeline - "it would have been GM101," Hellerqvist quips.

Hellerqvist considers himself indebted to GlycoMed's officers for the corporate cautionary tale; it made him resolve not to have his discovery meet the same fate as GlycoMed's carbohydrates. He arranged to have CM101 research continue in Vanderbilt's labs through phase I testing, which was carried out with a contract research firm. At the phase II point, the discovery would be licensed. "We managed to get through phase I clinical trials with the scientists still owning the company," Hellerqvist says.

The corporation's funding was obtained the way most university research collaborations are arranged - at scientific meetings. A member of the Hellerqvist team made a presentation, a "guy interested in putting together a research boutique" heard it, and venture capital was thereby secured, Hellerqvist says. With Zeneca, the negotiations were also initiated by contacts made at scientific conventions. Hellerqvist knew he didn't want to take on cancer: "It's too big," he says. "We wanted to license cancer and rheumatoid arthritis right away."

CarboMed will keep for itself the spinal cord indication, as well as other niche clinical areas such as work on keloids, the abnormal scarring sometimes seen in wound healing. These applications of CM101's potential do not cost as much to test, Hellerqvist notes; with an acute spinal injury, for instance, the drug's efficacy can be determined in two to three months. The deal with Zeneca allows CarboMed to continue its niche research and collect payments while its partner explores bigger markets. It is CarboMed that will test CM101's potential to help the approximately 10,000 Americans each year who incur spinal cord injury - including any country singer who wrecks his truck.