For some scientists, the “eureka!” moment comes early and easily. Others labor for years until the right combination of persistence and circumstances collide. William J. Whelan, D.Sc., is one of the latter.

Whelan, professor of biochemistry and molecular biology and chairman emeritus of the University of Miami Miller School Of Medicine’s Department of Biochemistry and Molecular Biology, began researching starch and glycogen synthesis in 1950.

Glycogen is a stored form of glucose, or sugar, used by the body for energy and for maintaining the level of blood glucose. Whelan’s discovery of glycogenin provided the missing link in the biosynthetic pathway for how glucose is turned into glycogen, the answer to a puzzle that had baffled other investigators for a century. His work and the techniques he developed for isolating and characterizing molecular structures like glycogen have become scientific standards.

“I’m a great believer in luck, and I find the harder I work the more I have of it.” —Thomas Jefferson

In 1992 Whelan was named a fellow of the Royal Society, one of the highest honors granted in the scientific community. In 2006 he received the University of Miami’s Distinguished Faculty Scholar Award for lifetime achievement in research. In the five decades between launching his research and receiving this distinguished recognition, he endured skepticism, dead ends, and lost funding. Today, Whelan’s discovery of the primer for glycogen synthesis is an accepted principle included in almost all biochemistry textbooks. He credits his accomplishments to determination, talented colleagues, and just plain good luck. “This is a story of serendipity—a succession of lucky experiences every practicing scientist will be familiar with,” Whelan says.

Luck has been with Whelan his whole life, he says. The eldest of four children raised near Manchester, England, during the Depression, he was lucky enough to have a teacher in school who cultivated his interest in biochemistry. Whelan’s father, an immigrant from Ireland, made the skins for sausages; his mother was a housewife. Whelan became the first in his family to pursue a higher education.

Whelan received one of three countrywide scholarships from the Brewer’s Society for the University of Birmingham, where he was to study the science of brewing. But here serendipity intervened: World War II had arrived, and the scholarship recipients would have to enroll in the army unless they studied chemistry instead of brewing. “We did not have freedom of choice of topic for our beginning graduate studies and were allocated them apparently at random. A school friend who had come with me to Birmingham, also with the intent to become a biochemist, was put to work on something that only after the war was over did we get to know was part of the Manhattan Project [the secret U.S. project to create the atomic bomb]. He never did become a biochemist,” Whelan recalls.

Whelan was put to work with the Royal Navy on an antisubmarine detection device, the Asdic Recorder, which is still used in the fishing industry today. After the war ended, while still a graduate student, Whelan became a member of the university’s faculty, “free to pursue my desire to become a biochemist.” He began to focus on the enzymology, or the biochemical nature and activity, of glycogen and starch.

‘There Still Seemed to Be Plenty to Do’

Before she passed away in 1993, Whelan’s wife, Margaret, used to greet him as he returned home, “Discover anything nice today?” For a long time, Whelan had to answer in the negative.

He spent several frustrating years pursuing an angle in the study of glycogen and starch “that had to be right—we knew it had be right,” but that fellow scientists and funding agencies, including the National Institutes of Health (NIH), said was absolutely wrong.

Enzymes (mostly proteins) control metabolism. “Enzymes bring about the chemical transformations of life, outside and inside the cell,” says Whelan.

“My aim was to use enzymes to explore the structures of large carbohydrates, such as starch, and its animal counterpart, glycogen.” New technology that was just becoming available enabled Whelan to prepare a series of small molecules of known structures that he could use in order to learn how they were broken down by the starch-splitting enzymes. With that knowledge, he could now use the enzymes on starch and glycogen.

When Whelan first began working on glycogen and starch, Carl and Gerty Cori had won the 1947 Nobel Prize in Physiology or Medicine for their synthesis of glycogen, the process by which the body converts glucose into glycogen, the form in which sugar is stored. They identified and purified a number of the enzymes involved in glucose metabolism, and their work ultimately advanced scientific understanding of metabolic regulation.

“I recall in the ’50s being asked what I was working on. When I replied glycogen and starch, the response, as often as not, having in mind the Cori discoveries, would be: ‘But that’s all sewn up!’” So in effect, Whelan had “unwittingly entered a field of research that was considered a dead end.

“I was not put off by this. There still seemed to be plenty to do,” Whelan says.

So in 1963 Whelan persuaded the CIBA Foundation (now known as the Novartis Foundation) to organize a symposium in London to explore findings in glycogen research. The historic meeting, which brought together past and future Nobel Prize winners along with other top scientists, showed “that the field was far from moribund.” Inspired by the discussions of glycogen, Whelan began searching for the missing component of the glycogen synthesizing system, the primer that would switch on glycogen synthesis.

“It’s the equivalent to an ignition key in an automobile—the engine won’t turn on unless the key is turned,” Whelan explains. Similarly, glycogen synthesis would not occur without a primer to set the process into motion.

Whelan and other scientists disproved the previous theories of primers that had floated about in the aftermath of the CIBA Foundation symposium. But they also lacked any new notion about what might be triggering the process.

Working with international collaborators, Whelan began to pursue the idea that the primer was a protein, and not, as had been supposed, a carbohydrate. In 1980 a young biochemist named Joseph Lomako, who was visiting Whelan’s lab for a year, succeeded in isolating the protein from glycogen. They named it glycogenin.

After such a significant discovery, Whelan fully expected the NIH to renew the funding that had paid for this research. He was wrong.

First Denied, then Celebrated

In 1967 Whelan, then a world-renowned scientist, joined the faculty at the University of Miami Miller School of Medicine. “Bill Whelan represented the beginning of major credibility in the basic sciences for the School of Medicine when he arrived in 1967,” says Lawrence M. Fishman, M.D., professor emeritus of medicine. “He was a very well-recognized scientist before he came here,” says Bernard Fogel, M.D., dean emeritus of the Miller School. But despite his reputation and renown, Whelan’s glycogenin discovery was roundly rejected.

For seven years, from 1980 to 1987, the NIH disagreed with Whelan’s lab’s findings: “This reviewer is troubled by the repeated inferences that glycogenin is the primer for glycogen synthesis,” stated one NIH critique.

With a graduate student, Ignacio Rodriguez, Whelan resolved one issue, the answer to which the NIH had insisted on: Just what is the chemical bond between glycogen and glycogenin? It proved difficult to answer—because once elucidated, it turned out to be a bond that was previously unknown in animals. But even when this news was conveyed to the NIH, funding was still denied.

“This happens to everyone who comes up with a new idea,” explains Whelan. “People are just damn skeptical.”

But the time to convince people—most notably funding sources—was growing short.

Money began to run out for the project, which Whelan kept afloat for a time with small grants from industry for other projects.

But Whelan’s students were about to graduate, and the lab would be empty, without funds.

We Could So Easily Have Given Up’

At that point, Whelan’s wife Margaret came to his aid. As a faculty member in the United Kingdom, Whelan had accumulated a small retirement fund that he was entitled to when he reached 60. Margaret suggested spending that money on the lab. Whelan brought Joseph Lomako back to Miami. With Wie Lomako, Joseph’s wife, also part of the team, they were able to extend their findings and finally isolate pure, active glycogenin from muscle. “Glycogenin was proven to be the primer, an enzyme that acts on itself, like a surgeon operating on his own appendix. You cannot imagine the excitement of being the first to discover something that has been around for all eternity but never before revealed,” says Whelan.

With this, their work was accepted, and NIH funding was restored. Four years later, the Royal Society elected him a fellow, citing “the elucidation of the role of a protein primer in the biosynthesis of glycogen.”

“This allowed us to study the structure of glycogen normally and what it would be like in glycogen storage diseases (such as Pompe’s Disease and Cori’s Disease). We determined that the structure is abnormal in certain glycogen storage diseases, and from there we could deduce what’s wrong with the enzymes. Now we know what’s wrong with the genes in these diseases,” says Frans Huijing, Ph.D., professor of biochemistry and molecular biology, who was recruited to the Miller School of Medicine in 1968 by Whelan.

An Asset to the School

For 24 years Whelan served as chairman of the Miller School of Medicine’s Department of Biochemistry and Molecular Biology. He remains a professor of biochemistry and molecular biology to this day, teaching classes on both the medical and Coral Gables campuses. His tenure at the school is remarkable not only for his work in the lab but also in the committees, councils, and community of the young medical school, which was only 15 years old when he arrived.

Among his accomplishments were the creation of the Ph.D. to M.D. program, which ran from 1971 to 1988, and the founding of the Miami Winter Symposium, which will be holding its 40th meeting in 2007. The symposia bring Miller School graduate and postdoctoral students and faculty face-to-face with nationally and internationally prominent scientists, including several Nobel Laureates, each year. Since its inception in 1968, the symposia have only grown in popularity and are now one of the conferences sponsored by the renowned journal Nature.

“Add my voice to the mountains of praise for Bill Whelan’s role in putting the biochemistry department in Miami among the leaders in the U.S. He has done this by shrewdly exploiting your winter climate to fund winter symposia that are now a ‘must’ for ambitious young researchers. His other stroke of genius was to recruit biochemically oriented staff in other medical departments as honorary members of his own department. This built alliances that led to the groundbreaking success of your Ph.D. to M.D. program, which is universally admired. All this was on top of retaining his leading research role in the enzymology of carbohydrates,” says Brian S. Hartley, Ph.D., F.R.S., director for the Centre for Biotechnology in London’s Imperial College of Science and Technology.

In addition to those laurels, for over 40 years Whelan has been involved in international biochemical organizations, as the secretary general and president of three and the founder and first editor in chief of several of the most highly cited biochemical journals. These belong to the not-for-profit organizations on whose behalf Whelan has worked, and the royalties they have earned now run into tens of millions of dollars that support biochemists worldwide.

Now 82, Whelan has decided that he’s going to slow down, maybe step down from teaching and give up some of his academic responsibilities, though he’ll still continue his role as an editor in chief for the International Union of Biochemistry and Molecular Biology. However, “I think I’m going to gradually fade away,” Whelan says.

But Fishman, Huijing, and hundreds of other colleagues, collaborators, and present and past students can’t see that happening. “He is such a dynamic individual,” says Fishman. “Even in his eighth decade, he’s just beyond most of us intellectually.

“I think Bill Whelan is one of the most important people in our medical school. He was instrumental in having the School of Medicine become a respectable place to do research.”