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Nobel Prize honors two stem cell research stars

An old hand from Britain and a younger Japanese scientist profoundly altered beliefs about biology.

October 09, 2012|Eryn Brown and Jon Bardin
  • Dr. Shinya Yamanaka, who does research at the Gladstone Institutes in San Francisco, and British researcher Sir John Gurdon were awarded the Nobel Prize in physiology or medicine.
Dr. Shinya Yamanaka, who does research at the Gladstone Institutes in San… (Chris Goodfellow, Gladstone…)

Two scientists who upended fundamental beliefs about biology by demonstrating that every cell in the body has the potential to grow into every other type of cell have won the Nobel Prize in physiology or medicine.

Sir John Gurdon and Dr. Shinya Yamanaka were honored Monday for "the discovery that mature cells can be reprogrammed" to return to a very early state of development, the Nobel committee said in its citation.

For The Record
Los Angeles Times Wednesday, October 10, 2012 Home Edition Main News Part A Page 4 News Desk 1 inches; 57 words Type of Material: Correction
Nobel Prize: The headline on an article in the Oct. 9 Section A about the Nobel Prize in physiology or medicine said that the award went to two stem cell researchers. One winner, Dr. Shinya Yamanaka, is a stem cell researcher, but Sir John Gurdon is not. The two were honored for their work on cell reprogramming.

Their research is still years away from yielding a clear breakthrough in medical treatment. But the work has upended the study of intractable conditions including heart disease, diabetes and Alzheimer's by allowing scientists to grow disease-specific -- and even patient-specific -- cells for experimentation in the laboratory, experts said.

"It's nothing short of a revolution in how we think of a cell," said Dr. Deepak Srivastava, director of the Roddenberry Center for Stem Cell Biology and Medicine at the Gladstone Institutes in San Francisco, where Yamanaka works one week each month.

Gurdon, 79, performed his seminal work at Oxford University in the late 1950s and early 1960s -- a good deal of it before Yamanaka was born.

Working with frogs, he showed in 1962 that replacing the nucleus of an egg cell with the nucleus from a cell taken from a tadpole's intestine allowed the egg to develop into a fully functional clone of that tadpole.

The discovery shocked his colleagues in the field. At the time, it wasn't clear whether different types of body cells had different DNA or shared the same genetic instructions and just read them differently, Srivastava said.

Gurdon's experiments indicated that cells did contain the same genetic code and that individual cells were capable of creating an entire animal -- and thus any of its component parts -- if properly manipulated.

It would take 34 years for Scottish researcher Ian Wilmut to clone Dolly the sheep, replicating the feat in a mammal and capturing the public's imagination.

Yamanaka's achievement was to give scientists an idea of how that cellular reprogramming gets done. When he began this line of work, he was highly criticized in Japan for undertaking such a difficult project.

The Japanese scientist -- who trained as an orthopedic surgeon before becoming a full-time researcher -- figured out that activating simple combinations of genes in a mouse skin cell could rewind that cell to an embryo-like state, allowing it to develop anew as any other type of cell in the body.

Dr. Owen Witte, director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, was in the audience when Yamanaka presented his research to a meeting of biologists in Toronto in 2006. He said there was a gasp in the room when Yamanaka unveiled his breakthrough.

"Everyone knew we were hearing something that would change the history of science," Witte said. "We knew he would win the Nobel Prize."

Dr. Francis Collins, director of the National Institutes of Health, said that he too "got chills up and down my spine" when he read Yamanaka's paper describing his work, which was published a few months later in the journal Cell.

Until then, it was assumed that cell development was a one-way street. There was no way to "read that paper and not decide that the world was really changed," Collins said.

The cells Yamanaka created in mice -- and, a year later, in humans -- are known as induced pluripotent stem cells, or iPS cells.

Researchers around the world are now using Yamanaka's technique to transform cells from patients with a variety of ailments into iPS cells and then studying them to understand the mechanics of disease at a cellular level.

Scientists are also using the "disease in a dish" model to test new drugs.

"If someone has Alzheimer's, we can't take a biopsy of the brain," Srivastava said. "But we can take a skin cell, turn it into an iPS cell, and study that."

Soon, he added, work with iPS cells may allow physicians to deliver on the promise of personalized medicine.

Studies of patient cells could help doctors develop targeted drug treatments and determine what therapy is most appropriate in a specific case.

Further on the horizon, scientists hope to use the technology to regenerate replacement cells for patients, such as insulin-producing cells for those with Type 1 diabetes or neurons for those who have suffered spinal cord injuries.

Another goal is to treat diseased tissues directly by reprogramming cells into a healthy state.

Next year, a Japanese team will test the first iPS-based treatment for people to reverse an eye condition called macular degeneration, Yamanaka said during a news conference Monday. A trial of a cell-based treatment for macular degeneration using the more-controversial embryonic stem cells is already underway at UCLA and some other sites.

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