This article first appeared in the St. Louis Beacon, Feb. 14, 2011 - In 1978, no one knew that an almost invariably fatal, sexually transmitted disease was on the horizon. Nevertheless, it was the year Duane Grandgenett and a team of Saint Louis University scientists would discover an enzyme, integrase, that would be the key to developing effective treatments for HIV and AIDS. The serendipitous finding after decades of work was the result, Grandgenett says, of simple, basic research.
"I'm a basic scientist," said Grandgenett, a professor at the Institute for Molecular Virology at Saint Louis University School of Medicine. "I asked a very simple question no one else had asked, 'How do retroviruses integrate?'"
Basic 'Chicken Research'
Grandgenett modestly referred to his ground-breaking discovery, which earned him the title of the "father of integrase," simply as "chicken research." He first identified the integrase protein in avian retroviruses.
"He followed his scientist nose and stuck with it: old-fashioned, basic science," said Paul Loewenstein, a molecular virology professor at SLU who has known Grandgenett for 40 years. "But he recognized when he was on to something."
Grandgenett had discovered an enzyme that provokes the process that gives HIV a toehold on a person's DNA, where it quickly sets about replicating itself and wreaking havoc upon the immune system. Discovery of the retroviral integrase was a critical step in rapidly understanding the insidious HIV virus.
"Much more rapid than it would have been had he not been around," said William Wold, chair of the department of molecular microbiology and immunology at SLU. "Because of his work on the avian virus, when HIV was discovered, it enabled the AIDS field to make very, very rapid advances. Without basic research there would be no applied research with any rational application and no one would have been able to develop an anti-HIV drug."
From Lab to Lives
Grandgenett published 10 papers relating to his discovery of integrase. By the time HIV and AIDS were given names in 1986, pharmaceutical companies were developing medications made possible in part by his efforts.
Buttressed by Grandgenett's early and ongoing integrase research, new, more effective drugs with fewer side effects continue to be developed. More than 20 drugs that help to hold the invading virus in an inactive state are now on the market.
There is still no cure or preventive vaccine, but for approximately 33 million people worldwide who have HIV/AIDS, there is hope.
"The drugs have been very good," Grandgenett said.
So good, that the FDA in 2007 approved a drug called Raltegravir, the first in a new class of medications known as integrase inhibitors. The drug was developed by pharmaceutical giant Merck & Co., with whom Grandgenett had collaborated since 1994. Grangenett's work laid the foundation for the drug, which has become an important part of a multi-drug regimen for AIDS and has been found to be an effective primary therapy for the virus.
Grandgenett retains a reservoir of curiosity, so the research continues. He recently developed a new and potentially improved process to investigate second-generation integrase inhibitors to combat integrase mutants resistant to Raltegravir.
Grandgenett, 68, also continues to gain attention and support for his work the old-fashioned way: He publishes solid findings.
"Dr. Grandgenett is a pioneer, gentleman," said Opendra Sharma, a basic sciences program officer with the National Institutes of Health, who has overseen Grandgenett's grants for 20 years. "He's the kind of guy who doesn't make much noise. He just works on a problem and step by step ... He never publishes half-baked stories."
Farm Boy Becomes Scientist
Words like "integrase" weren't in Duane Peter Grandgenett's vocabulary when he was growing up in Bancroft, Iowa, a half-mile square farming town. But it's where his scientific interest was piqued. Where others saw just corn and soybeans, Grandgenett saw nature unfolding and wondered about the miraculous growth process.
"I was just generally interested in science and biology and how things grew," Grandgenett said. "I've always been interested in my environment -- how you go through the whole cycle of growth and death."
He was also interested in a world outside of the farm and his mother, who still lives in Bancroft, encouraged him to explore that world.
"So I did, and I never went back," Grandgenett said.
His parents weren't able to send him or his two brothers and sister to college, so Grandgenett worked his way through after graduating from St. John's Catholic High School, where an excellent Sisters of St. Francis science teacher had further stimulated his interest.
After high school, he attended trade school to become a medical technologist. It enabled him to get a job in a hospital lab that paid his tuition at community college. Grandgenett transferred to Mankato State University in Minnesota, where he received a B.S. in chemistry. He went on to receive his M.S. and a Ph.D. in microbiology from the University of Iowa.
He has been at Saint Louis University's Institute for Molecular Virology since he arrived as a postdoctoral fellow in 1971, steadily climbing the ranks and doing the work he loves, inside and outside the university.
In addition to collaborating with Merck, Grandgenett has served as a reviewer on numerous NIH studies -- from experimental virology to the National Science Foundation and groups conducting research related to HIV/AIDS.
He has presented to organizations such as the NIH, the International Conference on HIV Integrase and the Australian Centre for HIV and Hepatitis Virology -- and to local student groups.
"You have to reach them as young as you possibly can," Grandgenett said.
At every stage, he has mentored: postdoctoral fellows, graduate and medical students, undergraduates and high school students who he brought into the lab. For a decade, he served as director of Saint Louis University's Cell and Molecular Biology graduate program.
"He's a marvelous mentor to his students," Loewenstein said. "He clearly strives to make sure that students understand what he's trying to teach them. He assists them to make their own discoveries by encouraging them to think."
Putting Down City Roots
Although he never returned to farm life, Grandgenett never lost the yearning.
"I think a farm is the best place to be; I wish I could have raised my kids on a farm," he said wistfully. "It's a very nice life. Farmers are independent people who do what they want and work hard."
Grandgenett has been married to Jean, his high school sweetheart, for 48 years. They have two daughters, a son and six grandchildren.
They live in Brentwood in the same house they've lived in since 1970.
"It's a nice house," Grandgenett laughed. "And the kids didn't want to move, so we stayed there."
Science for the Joy of It
Grandgenett says he has never been alone in his achievements, noting that his SLU colleagues and literally thousands of scientists and investigators have contributed to his work and many accomplishments.
But he is proud to be honored by colleagues from time to time. Among his awards is the Faculty Research Award from the American Cancer Society, and he will be receiving the Fellows Award for Outstanding Achievement in Science from the Academy of Science-St. Louis on April 13.
"Science is a community," Grandgenett says. "To solve problems, it takes many people. It takes many, many minds to solve a problem because Mother Nature is really, really tough."
Tough or not, Grandgenett has made a singular contribution for which he has garnered worldwide acclaim. That's not, however, what motivates him.
"I just do the science for the joy of it," Grandgenett said. "You do science to help people. If you have a good discovery, it spreads all over the world."
Gloria Ross is the head of Okara Communications.