Dr. Robert Vince - 2010 Inductee
Dr. Robert Vince, Director of the Center for Drug Design and Professor of Medicinal Chemistry at the University of Minnesota, is a leader in the field of drug research. He holds 25 patents on antitumor and antiviral agents and has co-authored over 160 scientific publications. His work has had a transformative impact on the treatment of Herpes infections, AIDS/HIV, and other critical diseases.
His first interest in pharmacy and medicinal chemistry stems from a summer job behind a pharmacy counter. “I was interested in science and chemistry from a young age, and later developed an interest in medicine,” he explained, “and medicinal chemistry incorporates the understanding of drug development by combining chemistry, biochemistry, molecular biology, and pharmacology into one discipline.”
After obtaining his pharmacology degree in 1962 and his doctorate in medicinal chemistry from the State University of New York, at Buffalo in 1966, he was attracted to the relatively new field of antiviral medicine. Scientists had only recently begun to explain the behavior of viruses, and the first antiviral compounds emerged from other research. While working with anticancer agents, scientists discovered that nucleotides - the basic components of DNA - could be chemically altered to disrupt the reproduction of a virus.
While it is highly unusual for any drug candidate from an academic laboratory to survive the extremely competitive pharmaceutical drug development process, Vince has been instrumental in the design of two drugs developed for commercial use.
With his Ph.D. advisor, Dr. Howard J. Schaeffer, Vince developed the first acyclonucleoside family of drugs that would eventually lead to the development of Acyclovir (pronounced a-SYE-klo-veer), the standard treatment for Herpes, upon Schaefer’s later move to the Burroughs Welcome Pharmaceutical Company.
His most recent achievement is the development of “carbovirs,” a series of carbocyclic nucleoside antiviral drugs used in the development of Ziagen® (pronounced zy-uh-jen). It is one of the leading anti-HIV drugs used marketed worldwide for the treatment of AIDS in adults and children.
Like most members of the research community, in the mid-1980s Vince began hearing about AIDS (the acronym for acquired immune deficiency syndrome, a disease in which the sufferer loses immunity to infection and some forms of cancer). HIV (human immunodeficiency virus, a retrovirus which causes AIDS) inserts itself into human cells, then, with an enzyme called reverse transcriptase, the virus replicates itself as many as 1 billions times every 24 hours. Reverse transcriptase is an enzyme protein contained in the virus and is used to produce DNA molecules that the virus needs to reproduce itself. HIV behaves differently from previously known viruses, depressing the body’s immune system and mutating so quickly that attempts to understand its reproductive mechanism - much less defeat it - could hardly keep pace.
Following the identification of HIV as the cause of AIDS, an intense effort was made to identify drugs for the treatment of this debilitating, lethal disease.
After a decade of research into the behavior of viruses, Vince knew that altered nucleosides could act as chemical decoys, stopping reverse transcriptase from commencing the DNA replication process of HIV, and thus effectively neutralizing the virus without destroying healthy cells.
At the University of Minnesota, Vince and Dr. Mei Hua, a visiting scientist from China, working in Vince’s laboratory, synthesized a series of new nucleotide compounds they called "carbovirs.” The compounds were sent to Alabama’s Southern Research Institute where they were screened under an NIH program to find anti-AIDS drugs. They proved effective in inhibiting the replication of HIV, while showing low toxicity to human cells - meaning that they were good candidates for anti-AIDS drug development. The data were sent to NIH where the compounds were retested.
“I remember that an NIH scientist, Dr. Robert Shoemaker, phoned me at home on a Saturday morning,” Vince recalls. “He was really excited and told me they wanted me to patent these compounds right away, and that they would fund all preclinical testing required to attract a pharmaceutical company for development.”
The University patented the compounds, crediting Vince and Hua with the discovery. Drug companies were eager to develop antiviral therapies. Even so, it took a decade for Vince's compounds to become a marketable drug.
The University licensed the patent for carbovirs to the London-based pharmaceutical giant GlaxoSmithKline in exchange for five percent of sales from the drug developed into the anti-HIV drug, Ziagen®. This drug has resulted in hundreds of millions of dollars of sales for GlaxoSmithKline and over $400 million in royalties for the University of Minnesota.
As mandated by federal law, two-thirds of the royalties must be reinvested in research - in this case, an endowment for graduate students and a new drug-development center. The University established a Center for Drug Design, with Vince as its director. The Center has already gained international reputation for excellence in medicinal chemistry research. Vince is putting his share of the royalties to work developing new AIDS drugs and other potential drug candidates for a variety of diseases at the Center.
For 35 years Vince has taught medicinal chemistry to undergraduate pharmacy students, medicinal chemistry graduate and postdoctoral students at the University of Minnesota. He has advised a large number of doctoral and postdoctoral students in his laboratory, who have gone on to very productive careers.
NOTE: This short biography has been compiled from information in the nomination form submitted to the Minnesota Inventors Hall of Fame, selected quotations from Dr. Vince, and information available on the Internet and from a variety of other sources.
Post Script: The following comments on background were received from Dr. Vince following notice of his selection for induction:
Born: November 20, 1940 Auburn, New York
My mother and father were hard workers and were limited in their formal education, as so many immigrant families were at that time. Both had to quit school after the eighth grade to help support their families. My mother’s parents emigrated from Italy in the early 1900s. My father’s father also came here from Italy, and his mother came from Poland at about the same time. My paternal grandparents spoke Polish in their home, and my maternal grandparents spoke Italian.
My father had many different jobs while I was growing up, including factory work, welder, salesman, and owner of a mom and pop grocery store for many years until the super market stores arrived and became too competitive. My mother also worked in various local factories doing mostly piecework sewing.
I was always interested in experimenting when I was young. When I was twelve, my father gave me his wooden grocery store counter for a lab bench, and diverted gas from our basement gas pipe to a Bunsen burner for my lab. I started with a Gilbert Chemistry set, and was able to get chemicals from a Gilbert catalog. Chemicals such as potassium permanganate or powdered magnesium would not be available in chemistry sets today. The local drug stores were also a good source of chemicals. I didn’t have much in the way of equipment, such as weighing balances, flasks, measuring and mixing devices, etc., so I had to improvise.
One day, while trying to make rocket fuel, I was mixing various amounts of chemicals in a large mortar while guessing the weight of each ingredient. To periodically check my mixture for the proper burning rate, I took small samples out of the mortar and ignited them on the bench. One sample burned too rapidly and a spark flew into the mortar and ignited the whole sulfur-containing mixture. The smoke bellowed up through our heating registers and filled our house with sulfur fumes. My mother was on the phone and began screaming that the house was on fire. Although no fire occurred, I was subsequently forced to move my lab to the detached garage.
My early interest in chemistry and physics required reading many books on these subjects before taking formal courses. Like many scientists of my generation, I was inspired at an early age by several books, especially “Microbe Hunters,” by Paul deKruif and “Crucibles: A Story of Chemistry” (I can’t remember the author, but a later edition was authored byu Bernard Jaffe). I was really more interested in physics than chemistry, and read everything I could find on the Manhattan Project. In junior high, I made a Wilson Cloud Chamber to observe ion paths left by radio particles, and also made a VandeGraaff electrostatic generator. These projects took place in my bedroom, where I had a small physics lab. I always felt that I would make a better chemist than physicist, and anyway, all the fun stuff in physics had already been done (at least that’s what I thought).
At the time I applied for college, I wasn’t aware of the opportunities available for someone with my interests. Most high schools didn’t have career councilors in the fifties. Since I was interested in chemistry and also medicine, but was not interested in being a physician, Pharmacy seemed to provide a start in that direction. I worked in a drug store while in high school, and the idea of being a pharmacist appealed to me. After attending one year of pharmacy school, I decided that laboratory research work would be more challenging. My pharmaceutical chemistry (now called medicinal chemistry) professor let me work in his lab and assigned me to solve a chemistry problem that he encountered while previously working in a pharmaceutical company. I solved the problem and published two papers in the Journal of Organic Chemistry (entitled “Molecular Rearrangements of Cyclic Beta Diketones”) in my junior and senior years.
After receiving my pharmacy degree, I continued to do research in medicinal chemistry. I selected a more biologically related project and wrote my Ph.D. thesis on the design of modified nucleosides to test their ability to block enzymes that produce DNA. This work led to my interest in anticancer and antiviral agents and mechanisms of DNA reproduction.