Stowers Explores the Mysteries of Life

Ask any physician, professor, or researcher involved in the life sciences in the Kansas City area, and they'll tell you that the founding of one organization has set the region's life science research on fire. That organization is the Stowers Institute. And it all began with two peple and a shared vision. In 1994, Jim and Virginia Stowers set up an endowment to establish the not-for-profit research institution, and they recently added an unprecedented $1.1 billion to it, bringing the total investment up to $1.6 billion.

"For two individuals to make this level of financial and philosophical commitment to the life sciences is truly extraordinary," said HBC executive director Charles Decedue. "There's no question, it will revolutionize the Kansas City area and the industry." Jim Stowers, a University of Missouri medical school graduate and founder of KC-based American Century Investments, and Virginia Stowers, a nurse by training, have structured the endowment in such a way that 100 percent of the money goes toward funding basic life science research.

"Since both Jim and Virginia have a medical background, and both have survived cancer, they decided that the best way to find cures for disease is to support basic research into the genes and proteins responsible for the fundamental processes of cellular life," said Stowers Institute CEO William Neaves. "They have the conviction that once you know enough at that most basic of levels, you'll gain fundamental insights into preventing and curing disease." Neaves came to Stowers from the University of Texas Southwestern Medical Center in Dallas.

Not everyone believed that Kansas City could support a world-class medical research institute. However, the new 10-acre campus at 50th and Rockhill has silenced the naysayers. Neaves said, "Without a doubt, Jim and Virginia have created the finest molecular genetics laboratory facility in the world." The science building just opened last fall and is now housing the researchers that the Stowers Institute is actively recruiting. Neaves anticipates filling the campus with 600 researchers by the end of 2004, an astounding projection since, after more than 40 years of existence, the renowned Scripps Research Institute has a staff of 2,800. The Stowers Institute is in the process of hiring 50 independent scientists. Each scientist will then assemble a 10-15 person team of researchers.

Neaves said the working environment that Jim and Virginia have fostered is unique. "They are committed to making the Institute an exceptionally collegial and cordial environment for scientists who enjoy working together and who share the satisfaction of each other's accomplishments."

This supportive environment has given rise to a number of exciting research initiatives. For example, the Stowers Institute is making a major investment in fruit-fly genetics. They actively recruited and hired Kent Golic, the first person to demonstrate the ability to do homologous recombination and create targeted gene "knockouts" in fruit-flies. By systematically knocking out human disease-causing gene homologues in fruitflies, researchers can gain important insight into their function.

Neaves said that researchers are trading on the insight gained from the recently completed human genome project. In the fruitfly, researchers have found 177 genes similar to genes that are known to be involved in major human diseases. For more than a century, fruitflies have been a favored genetic model because they allow for quick and economical experimentation. Also, fruitflies lack much of the gene duplication normally found in mice and humans. "When you knock out one of the genes of interest," Neaves said, "then you're very likely to see the effect revealed in the phenotype of the fly because it's not masked by duplicate genes in the genome."

The Stowers Institute has also hired an outstanding young stem cell geneticist, Ting Xie, from the Carnegie Institute of Embryology at Johns Hopkins University. He is working with fruitflies to define the elements that maintain the undifferentiated status of stem cells. He is examining both genetic factors and the influence of the local environment within the organs and tissues where stem cells are found in determining the maintenance of this undifferentiated state.

"We're interested in learning as much as possible about stem cells so that we can compare them with cancer cells that multiply and remain undifferentiated," said Neaves. "We want to know how stem cells are caused to enter a particular differentiation pathway that results in their becoming a heart cell or a neuron, for example. Obviously, we also have interest in the potential ability to regenerate damaged tissues through the understanding of stem cell genetics."

Joan Conaway, a researcher who left a Howard Hughes Investiga-torship to come to Stowers, is investigating the molecular mechanics of gene transcription. "Her work is central to our interest in the role of genes and their protein products in causing susceptibility to disease," said Neaves. "We hope to understand more about how gene expression is controlled and what turns genes on and off."

The Stowers Institute also recently hired Scott Hawley, an international leader in the study of genes that influence miosis, or the division process that occurs in cells that are going to become oocytes or sperm. Hawley is a former Searle Scholar and the author of a popular book entitled The Human Genome: A User's Guide.

The scientific director of the Stowers Institute, Rob Krumlauf, was recruited from the National Institute of Medical Research, En-gland's equivalent of the National Institute of Health. He is well-known for his discoveries of HOX genes, which are responsible for axial patterning and brain development in the embryo.

It's just this kind of basic research that Jim and Virginia expect will have great relevance to a wide variety of human diseases. Simply put, their goal and the goal of the Stowers Institute is to explore the fundamental mysteries of life and, in the process, find ways to prevent and cure human disease.