Pioneer in biomedicine

Jacques Baenziger seems to be hooked on trying new things.

Many people are fond of flaunting the latest fads in clothing, technology, hobbies or foods, but Baenziger evinces a much deeper commitment to novelty: He signs up for first-of-their-kind ventures that last for years.

From attending an experimental college in Florida to breaking in the new M.D./Ph.D. program at Washington University to his field of scientific research — an important area of biomedicine long set aside as just-too-hard-to-pin-down — Baenziger always seems to pick the route where, he says, there’s “no road map and no idea if anyone’s going to succeed.”

“I admit it, I’ve had a kind of peculiar path,” says Baenziger, M.D., Ph.D., professor of anatomic and molecular pathology and of cell biology and physiology. “But if something looks like a good opportunity to me, I take it.”

New country, school

Baenziger didn’t have much of a say at the time, but this trend can be traced back to the first year of his life. Baenziger was born in Vevey, Switzerland. When he was a year old, his father, an engineer who worked for Nestle at its headquarters in Vevey, was offered a chance to go to Stamford, Conn.

“They were moving a division to the United States,” Baenziger says. “The head of that section offered my dad the opportunity to come over, and being fairly adventurous people, he and my mom decided to do it. It was a pretty gutsy move.”

When Nestle moved the division back to Switzerland years later, Baenziger’s parents decided to stay in the United States, even though it meant giving up his father’s pension, because they thought it would give their son more opportunities educationally and professionally. They moved to Tennessee, where Baenziger had a bedroom with a “spectacular” view of the Great Smoky Mountains.

After graduation from high school, Baenziger enrolled in New College of Florida, in Sarasota, where the main building was the former mansion of the Ringling Brothers of circus fame. Baenziger was a member of the third class at the new university, which was not yet accredited and gave no grades but had famous faculty members like Arnold Toynbee, a well-known historian.

“I can remember being one of only one or two students in organic chemistry class,” he says. “That was great because I was basically doing synthesis projects for the professor. But it was also intimidating because whenever he asked a question, I had no one to hide behind.”

A tricky transition

Unfortunately, having no class grades made getting into medical school tricky. Baenziger did well enough on his MCATs to be accepted at Johns Hopkins University but couldn’t get a scholarship there.

A professor recommended checking with WUSTL, which was just starting a new M.D./Ph.D. program.

“They already had the two students they were going to take, and those were all they could afford to support,” he says. “But I made a deal with the head of the program, Luis Glaser, Ph.D., then professor of biological chemistry, where I said I’d pay for my first year myself, and if I did as well as or better than the others in that first year, they’d start supporting me from then on.”

Baenziger won his bet, and, in 1975, he became one of the first WUSTL M.D./Ph.D. graduates. As he looks back, he marvels at how much he learned, not just in human biology and science, but also in terms of the limits of the human brain and the 24-hour day.

“There’s sometimes an expectation when you go into an M.D./Ph.D. program that you’re going to be excellent at absolutely everything,” he says, laughing. “That doesn’t always work out.”

Baenziger, who remembers having to “beg for a little less enrichment” during graduate school, says the secret is to recognize what is most interesting and potentially professionally useful in the huge array of knowledge and training that the M.D./Ph.D. program offers.

“Of course, you still have to be competent in the other areas, but, at some point, you have to decide that there are things you like more and are going to put more effort into,” he says. “Eventually, it clicks, and I guess that’s called maturity.”

Sugars’ contributions

The area that clicked for Baenziger under the mentorship of Stuart Kornfeld, M.D., Ph.D., now the David C. and Betty Farrell Professor of Medicine, was the study of how sugars and other carbohydrates affect biology. Known as glycobiology, this field, like many of Baenziger’s ventures, is rife with novelty and uncertainty but also deep with potential for new insights.

Added carbohydrates are the most common alteration to proteins after they have been assembled from instructions in DNA. Nearly all the proteins in the blood and on the surface of cells have sugars attached. The changes these sugar attachments cause in the properties of proteins may help explain one of the biggest mysteries of biology: why humans have many fewer genes than biologists expected. If adding different sugars allows cells to do two or more jobs with one protein, then the cell needs fewer genes.

Although this idea is widely accepted, it has been difficult for glycobiologists to demonstrate. Unlike proteins, sugars aren’t built from an explicit set of stored instructions. Sugars’ chemical structures are large, have much greater potential for diversity than proteins and often are more flexible and prone to move about. The consistency of the sugar attachments can vary, too: Depending on a variety of factors, the sugars may almost always, sometimes or only occasionally be added to a protein.

Baenziger, who has worked on these problems for more than three decades, found a unique set of sugars consistently added to certain reproductive hormones made by the pituitary gland. He identified the enzymes that add the sugars to the hormones and showed that disabling one of those enzymes led to a sharp increase in fertility in mice.

“One could imagine that, if down the road you have people who have fertility problems, it could be partly related to a defect somewhere in this very complicated system, and we might think about trying to modify it,” Baenziger says.

Baenziger was recognized with glycobiology’s highest prize, the Karl Meyer Award, in 2002.

“He went from A to Z in working out a very important pathway that represents a major milestone in the field,” Kornfeld says. “He did it in a careful and innovative way that led to the development of methods that are of much use to many other people who work in this area. He represents what a true physician/scientist should be.”

‘Renaissance guy’

Graduates of the Baenziger lab describe him as an outstanding mentor.

“Jacques was a great role model for M.D./Ph.D. students, particularly in helping us understand how basic research interfaces with clinical research,” says Eric Green, a 1994 M.D./Ph.D. graduate of the School of Medicine.

Green, now scientific director of the National Human Genome Research Institute, remembers “lots of laughter, camaraderie and serious science” in the Baenziger lab.

Karen Colley, Ph.D., a 1987 doctoral graduate who is now a professor of biochemistry and molecular genetics at the University of Illinois at Chicago, says she admires both Baenziger’s mentoring and the diverse array of personal hobbies he is involved in outside of the lab.

“Jacques is a real Renaissance guy, what with his interests in scuba diving, underwater photography, collecting orchids, sailing and classical guitar,” she says. “I hope when I get past the kid-raising stage, I can do fun things like he does.”

Baenziger is married to Nancy Baenziger, Ph.D., associate professor of neurobiology, whom he met while on his first interview for the M.D./Ph.D. program at WUSTL.

“She teaches the first-year medical school course on histology, and I teach the second-year course on pathology, so she shows them what it’s supposed to look like, and I show them what it looks like when it’s messed up,” Jacques Baenziger says with a chuckle.