The Duke community congratulated its first standing professor to win a Nobel Prize Wednesday, but two other Nobel Prize winners are appreciated here among the scientists who utilize their work.
Sir John Gurdon and Dr. Shinya Yamanaka were awarded the Nobel Prize in physiology or medicine Monday for their discovery that mature cells can be turned into stem cells. Their discovery opened up new ways for doctors at Duke and elsewhere to treat diseases including Parkinson’s disease, diabetes and heart disease, and allows scientists to gather stem cells without taking them from an embryo. The scientists will share the $1.2 million award.
“This is exciting because this opens the door to tissue engineering, where you can take cells from an individual,” said Dr. Vann Bennett, James B. Duke professor of cell biology, biochemistry and neurobiology. “Say you need to replace the cells in your heart. In principle you could take a cell from your skin and turn it into a heart cell and replace the damaged heart cells.”
Stem cells are unspecialized cells that have the capacity to develop into a variety of different cell types. This versatility means that they can become specific cells to repair damaged tissues in organs, a key step in fighting certain diseases. Gurdon and Yamanaka researched the process for taking adult cells and giving them the characteristics of stem cells. The products of this process are called induced pluripotent stem cells.
The discovery of iPS cells is a culmination of 50 years of work for Gurdon. In 1962, he conducted an experiment and discovered that he could take cell nuclei of a frog, implant them in a frog egg that had its nuclei removed, and create healthy new tadpoles.
“Gurdon’s experiment was not believed by people at the time because the central dogma was that once cells are differentiated, they could not go back,” Bennett said. “His experiment set the stage for the principle that differentiated cells are not a one-way trip.”
In 2006, Yamanaka expanded upon Gurdon’s work and performed an experiment that created mouse stem cells from adult mouse cells by inserting four specific genes. Through his experiment, he identified the genes that are able to convert a differentiated cell into a versatile stem cell.
“Yamanaka’s discoveries in 2006 were transformative,” Bennett noted. “He demystified the process of this differentiation of cells and put a molecular framework around it.”
Brigid Hogan, chair of the department of cell biology, said Yamanaka’s discovery took great insight and courage.
“I don’t think anybody really believed that it would be possible to take a cell and induce the expression of particular genes to make it reprogram into a pluripotential cell in a cultured dish,” Hogan said. “It was absolutely astounding. Everyone was taken by great surprise that it worked.”
One of the powerful uses of the discovery is modeling the development of human disease, which is especially useful for understanding neurodegenerative diseases, which lead to the decline or death of neurons. Scientists use iPS cells as models of human disease to test if drugs will stop degeneration, Hogan said.
The iPS cells also provide a method to obtain stem cells without taking them from an embryo, which has been a hotly debated ethical dilemma. Scientists previously derived pluripotent stem cells in a process that required separating the inner cell mass of an embryo four or five days after fertilization.
Research going on at Duke makes use of the iPS cell approaches, said David Goldstein, director of the Center for Human Genome Variation. Duke now has an iPS cell core facility that reprograms the cells.
“We’ve given them fibroblasts—a kind of cell from the skin—from the patient with the disease,” Goldstein said. “We’ve found the mutation that causes the disease and have given them to the core to try to understand the biology of the disease.”
The core has been running at Duke for about nine months. Although there were others conducting stem cell research at Duke before, the core facility makes the technology systematically available to people studying disease, Goldstein noted. Although iPS cells have proven useful in understanding disease, some scientists are concerned that iPS cells share too much in common with tumor-forming cancer cells.
“[The possibility of cancer] is a real concern, but you have to start somewhere,” Bennett said. “Once the principle is established, then techniques can be modified and refined. Before these discoveries were made, this would have been considered science fiction.”
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