Reprogramming mouse cells "major leap"

WASHINGTON — Scientists have transformed one type of fully developed adult cell into another inside a living animal, an advance that could lead to cures for a variety of illnesses and sidestep the political and ethical quagmires that have plagued embryonic stem-cell research.

Through a series of experiments involving mice, the Harvard biologists pinpointed three crucial molecular switches that, when flipped, convert a common cell in the pancreas into the more precious insulin-producing ones that diabetics need to survive.

The feat, published online Wednesday by the journal Nature, raises the prospect that patients with diabetes, heart disease, strokes and many other ailments could eventually have some of their cells reprogrammed to cure their afflictions without the need for drugs, transplants or other therapies.

"It's kind of an extreme makeover of a cell," said Douglas Melton, co-director of the Harvard Stem Cell Institute, who led the research. "The goal is to create cells that are missing or defective in people. It's very exciting."

He said that although the process didn't cure the mice, "they were able to reduce their blood-sugar levels to near normal."

The work is "a major leap" in reprogramming cells from one kind to another, said one expert not involved in the research, John Gearhart of the University of Pennsylvania.

That's because the feat was performed in living mice rather than a lab dish, the process was efficient and it was achieved directly without going through a middleman like embryonic stem cells, he said.

The findings left other researchers in a field that has become accustomed to rapid advances reaching for new superlatives to describe the potential implications.

"I'm stunned," said Robert Lanza, chief scientific officer of Advanced Cell Technology in Worcester, Mass., a developer of stem-cell therapies. "It introduces a whole new paradigm for treating disease."

"I think it's hugely significant," said George Daley, a stem-cell researcher at Children's Hospital in Boston. "This is a very spectacular first."

Even the harshest critics of embryonic stem-cell research hailed the development as a major, welcome development.

"I see no moral problem in this basic technique," said Richard Doerflinger of the U.S. Conference of Catholic Bishops, a leading opponent of embryonic stem cells because they involve destroying human embryos. "This is a 'win-win' situation for medicine and ethics."

Melton and other researchers cautioned that many years of research lay ahead to prove whether the development would translate into cures.

Although the experiment involved mice, Melton and other researchers were optimistic the approach would work in people.

"You never know for sure — mice aren't humans," Daley said. "But the biology of pancreatic development is very closely related in mice and humans."

Melton and his colleagues painstakingly identified which genes were likely to trigger the cell switch by sorting through more than 1,000 genes and winnowing them to ones that played a role in the development of insulin-producing cells.

They found that by injecting viruses carrying three genes into mice, they could turn the pancreatic cells into beta cells that produce insulin.

Melton has started experimenting with human cells in the laboratory and hopes to start planning the first studies involving people with diabetes within a year. "I would say within five years we could be ready to start human trials," he said.

Stem-cell research has been plagued by political and ethical debates because the cells can only be obtained by destroying embryos, which has been opposed by President Bush and others who think that even the earliest stages of human life have moral standing.

Scientists last year shocked the field when they said they had discovered how to manipulate the genes of adult cells to turn them back into the equivalent of embryonic cells — entities dubbed "induced pluripotent stem" or "iPS" cells — which could then be coaxed into any type of cell in the body.

The new work allows scientists to skip the intermediary step of iPS cells and directly transform adult cells.

Doerflinger said the discovery was the latest evidence that research involving human embryos was no longer necessary.

Other researchers disagreed, saying it remains unclear which approach will prove most useful.

Information from The Associated Press and The Boston Globe is included in this report.