In 1962, Gurdon wowed the world of biology by cloning a frog via a clever technique. He transplanted the genetic material from an intestinal cell of one frog into an egg cell from another. The egg developed into a tadpole, showing that ordinary cells contain the entire genetic instruction manual for whole organism.
The experiment — which other scientists were slow to accept as valid — led in 1997 to the cloning of the first mammal, Dolly the sheep. Since then, scientists have cloned mice, dogs, cats, pigs, horses and cattle, although mutliple attempts to clone monkeys have failed, as have attempts to produce cloned human embryos. Cloned mice have become laboratory mainstays.
Gurdon, 79, is an emeritus professor at Cambridge University who still conducts research at an institute there bearing his name and was knighted in 1995 for his work in developmental biology. His frog experiments a half-century ago showed that scientists “should be able to derive any one kind of cell from another, because they’ve all got the same genes,” Gurdon said Monday at a London news briefing.
In 2006 and 2007, Yamanaka extended this insight by turning back time on individual cells from mice and humans. By sprinkling four genes on ordinary skin cells, Yamanaka discovered a virtual fountain of youth: Any cell, he found, could be reverted to an early embryonic state.
These “induced” embryonic cells behave much like the ethically contentious stem cells gleaned from human embryos. Like embyronic cells, they can be grown into many other types of tissues but without having to destroy any embryos.
The breakthrough offered hope that someday skin cells could be harvested from a patient, sent back in time to an embryonic state, and then grown into replacement tissues such as heart muscle or nerve cells.
A huge global research effort is working to develop pluripotent stem cells, as they’re called, into treatments for heart disease, some forms of blindness, Parkinson’s disease and many other disorders.
Because the cells made by the technique are genetically identical to the patient, the advance “may one day allow us to transplant rejection-proof tissues,” said George Daley, a leading U.S. stem cell researcher and director of the Harvard Stem Cell Institute.
Yamanaka’s work “has now expanded to hundreds of labs around the world [that] are exploiting the techniques to study virtually every kind of disease. The impact cannot be overstated,” Daley said.
Already, scientists are using such transformed cells to study “diseases in a dish” made from patients with Alzheimer’s, Parkinson’s and Huntington’s disease. Research teams have also found shortcuts to turn skin cells directly into muscle fibers and brain neurons.
The first human trials of induced stem cell therapies could begin next year, Yamanaka said during a news briefing Monday. He said these three diseases present an attractive target for the first tests.
On Monday, Yamanaka credited his co-laureate for making his advances possible. “This field has a long history starting with John Gurdon,” he said in a brief telephone interview posted on the Nobel Prize Web site. Yamanaka noted that he was born in 1962 — the year Gurdon published his pivotal frog experiments.
A surgeon by training, Yamanaka, who splits his time between Japan’s Kyoto University and the Gladstone Institutes in San Francisco, said treating patients has always been his aim. “My goal all my life is to bring this stem cell technology to the bedside, to patients.”
But the therapeutic potential of induced stem cells remains in question. Some experiments show that the cells may form tumors, prompting skepticism that they will ever be safe enough to treat heart disease, Parkinson’s disease and many other conditions in which specific cells of the body break down.
However, the Nobel committee in its citation said the dual “groundbreaking discoveries have completely changed our view of development and cellular specialization. Textbooks have been rewritten and new research fields have been established. By reprogramming human cells, scientists have created new opportunities to study diseases and develop methods for diagnosis and therapy.”