In what researchers view as validation of the field, the Nobel
committee on Monday recognized pioneering contributions to stem
cell science by John Gurdon and Shinya Yamanaka
In a testament to the revolutionary potential of the field of
regenerative medicine, in which scientists are able to create and
replace any cells that are at fault in disease, the Nobel Prize
committee on Monday awarded the 2012 Nobel
in Physiology or Medicine to two researchers whose discoveries
have made such cellular alchemy possible.
The prize went to John B. Gurdon of the University of Cambridge
in England, who was the first to clone an animal, a frog, in 1962,
and to Shinya Yamanaka of Kyoto University in
Japan who in 2006 discovered the four genes necessary to
reprogram an adult cell back to an embryonic state.
Sir John Gurdon, who is now a professor at an institute that
bears his name, earned the ridicule of many colleagues back in the
1960s when he set out on a series of experiments to show that the
development of cells could be reversed. At the time, biologists
knew that all cells in an embryo had the potential to become any
cell in the body, but they believed that once a developmental path
was set for each cell — toward becoming part of the brain, or a nerve or muscle —
it could not be returned to its embryonic state. The thinking was
that as a cell developed, it would either shed or silence the genes
it no longer used, so that it would be impossible for a cell from
an adult animal, for example, to return to its embryonic state and
make other cells.
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Alzheimer’s)
Working with frogs, Gurdon proved his critics wrong, showing
that some reprogramming could occur. Gurdon took the DNA from a
mature frog’s gut cell and inserted it into an egg cell. The
resulting egg, when fertilized, developed into a normal tadpole, a
strong indication that the genes of the gut cell were amenable to
reprogramming; they had the ability to function as more than just
an intestinal cell, and could give rise to any of the cells needed
to create an entirely new frog.
Just as Gurdon was facing his critics in England, a young boy
was born in Osaka, Japan, who would eventually
take Gurdon’s finding to unthinkable extremes. Initially,
Shinya Yamanaka would follow his father’s wishes and become an
orthopedic surgeon, but he found himself ill-suited to the
surgeon’s life. Intrigued more by the behind-the-scenes biological
processes that make the body work, he found himself drawn to basic
research, and began his career by trying to find a way to lower
cholesterol production. That work also wasn’t successful, but it
drew him to the challenge of understanding what makes cells divide,
proliferate and develop in specific ways.
In 2006, while at Kyoto University, Yamanaka stunned scientists
by announcing he had successfully achieved what Gurdon had with the
frog cells, but without using eggs at all. Yamanaka mixed four
genes in with skin cells from adult mice and turned those cells
back to an embryo-like state, essentially erasing their development
and turning back their clock. The four genes reactivated other
genes that are prolific in the early embryo, and turned off those
that directed the cells to behave like skin.
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Ovary Stem Cells Can Produce New Human Eggs)
By that time, researchers had already shown that cells taken
from embryos at their earliest stages could also yield such
embryonic stem cells, but Yamanaka rewrote biology by demonstrating
that it was possible to turn adult cells into stem cells — cells
that are now known as induced pluripotent stem cells, or iPS cells
— without the help of either an egg (and whatever factors within
eggs that influence early development) or an embryonic cell.
Taken together, Gurdon’s and Yamanaka’s discoveries have turned
fundamental biological concepts on their head. Their experiments
prove that every cell, whether young or old, in embryos or in
adults, has a similar ability to reprogram itself to become “young”
again, and thus capable of becoming any cell in the body. What’s
more, Yamanaka’s advance provided a practical solution to a thorny
issue plaguing researchers interested in pursuing stem cell
biology: that the only source of human embryonic stem cells are
embryos, which must be destroyed in the process — a problem that
was morally sticky enough to compel President George W. Bush to
issue in 2001 a ban on the creation of new stem cell lines from
excess embryos discarded during fertility treatments (the ban was
removed
by President Barack
Obama in 2009).
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Blindness)
Yamanaka’s method further brings the potential for each patient
to become his own resource for replacement cells closer to reality
— thus treating disease. Within weeks of Yamanaka’s published
report on his discovery in 2006, laboratories around the world had
adopted the “Yamanaka factors,” as they are called, to generate
abundant lines of stem cells from skin and other mature cells.
Within a year, Yamanaka had taken the next important step in his
research — applying his achievements with mouse cells to human
skin cells and turning them back to an embryo-like state.
“What we have is the discovery of a game-changer in terms of how
we approach human disease in the coming years,” Dr. Deepak
Srivastava, director of the Roddenberry Center for Stem Cell
Biology and Medicine at the Gladstone Institutes, where Yamanaka
completed a postdoctoral fellowship and remains a faculty member,
said during a press conference celebrating the Nobel announcement
on Monday. “In the next five to 10 years we are likely to see the
same technology regenerate organs and create new treatments in
regenerative medicine for many different human diseases.”
Indeed, just over a year ago, the first groups of human patients
received treatment with embryonic stem cells. In a clinical trial
designed to test the safety of the treatment, Sue Freeman and
Rosemary (who declined to use her real name for reasons of privacy)
became the
first patients to receive retinal cells that had been grown in
the lab from stem cells. Each woman suffered from a different form
of macular degeneration, and both were gradually becoming blind.
Their doctor, Dr. Steven Schwartz at the University of California,
Los Angeles, told them that the cells they received could stop
their disease from robbing them completely of their vision. But
there was also the chance that the cells would do nothing at all,
and possibly even cause them harm, by forming tumors or other
abnormal growths in the eye — a gamble that had to be anticipated,
given that the treatment was unproven and never before tested in
humans.
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A Stem Cell First: Using the ‘Dolly’ Method on Human Cells)
While Freeman and Rosemary are among the pioneers of human
embryonic stem cell research (a previous human trial
also using cells made from embryonic stem cells, to treat spinal
cord injury, was halted by the company sponsoring the studies for
financial reasons), it won’t be long before embryos may not be
needed at all. Using Yamanaka’s method, labs around the world have
generated lines of heart, brain, nerve and muscle cells made from
iPS cells from patients with diseases ranging from Alzheimer’s to
spinal cord injury and diabetes, all in the hope of understanding
where in development these cells go awry and how to develop new
treatments that address these aberrations.
Already, Yamanaka says that researchers at the Center for iPS
Cell Research at Kyoto University, which he heads, are preparing to
transplant retinal cells made from iPS cells into patients with
macular degeneration next year. “The biggest hurdle is safety,” he
told reporters during a teleconference about moving iPS cells into
the clinic. “Especially in regenerative medicine, you have to
double check that you won’t see any severe side effects in
patients. We need to confirm the technology is safe.”
The concern is that because iPS cells are made from already
mature cells that have been manipulated to become other types of
cells, they may interact with chemicals and other tissues once in
the body to form abnormal growths, or they may fail to develop into
the cells required to treat a disease. Studies by stem cell
scientists show that while iPS cells are, for the most part, nearly
indistinguishable from embryonic stem cells, they do show some
differences that aren’t fully understood yet.
(MORE: Stem
Cell Research: The Quest Resumes)
Still, the technology, as the Nobel Prize committee
acknowledged, represents a breakthrough in our understanding of
cellular development, and could provide the key to finally curing
disease such as diabetes or Alzheimer’s, in which patients suffer
from diseased or failing cells that could one day be replaced by
healthy ones they grow themselves.
“It’s spectacular that the Nobel committee recognizes the
contribution of these scientists,” says Schwartz. “I think it helps
the public get enthusiastic about regenerative medicine and to
catch up with the science.”
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on Stem Cells
Alice Park is a writer at TIME and the author of The
Stem Cell Hope, which details the contributions of leading stem
cell scientists, including Gurdon and Yamanaka, to the emerging
field of regenerative medicine. Find her on Twitter at @aliceparkny. You can also
continue the discussion on TIME’s Facebook page and on Twitter at
@TIME.
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