It took 50 years for the Nobel committee to
acknowledge one of the key developments in biology.
A nucleus from a tadpole's somatic cell
transferred into a frog's egg resulted in development of a normal tadpole (1); this
was the first clone ever made in a laboratory, way back in 1962, and Professor Sir
John Gurdon was the visionary scientist behind it.
Professor Shinya Yamanaka's work on induced pluripotent stem (iPS) cells was embraced and recognised by the scientific
community much more rapidly. It took him only six years to become a Nobel
in 2006, he identified four genes that are responsible for keeping cells in a pluripotent
state and used them to revert fibroblasts (a
type of skin cell) from an adult mouse into an embryonic-like state (2). Every scientist
who works in the stem cell field had no doubt that Yamanaka would eventually win
the Nobel prize and I can assure you that all of us were delighted that it happened
sooner rather than later.
Since Yamanaka's first report in 2006, cell reprogramming
technology has moved forward with almost unbelievable speed. Only a year after
the initial discovery using a mouse system, Yamanaka and Professor James Thomson
from the University of Wisconsin, independently demonstrated that the approach
works in human cells too (3,4). The same year, Yamanaka also showed that new
animals (mice) can be generated from iPS cells, and that those mice are fertile
and capable of producing healthy pups (5).
The power of this new technology lies not only
in cloning a whole organism but also in its potential for personalised therapy.
Only a year after Yamanaka's discovery, Professor Rudolf Jaenisch's group at
the Massachusetts Institute of Technology demonstrated that by using iPS cells in
combination with gene therapy it might be possible to remedy otherwise
incurable genetic diseases (6).
In Jaenisch's experiments mice carrying the mutation
for sickle cell anaemia were successfully treated with iPS cells generated from
their own skin. Before being used for treatment, the iPS cells had the mutation
corrected using gene recombination technology. The cells were then differentiated
into hematopoietic cells and injected back into the animals. Already in 2009, a similar
approach has been used experimentally against another devastating disease, Fanconi
anemia, in a human in vitro system (7).
Given the various legitimate and less legitimate
safety concerns, the most prominent role for iPS cells at the moment seems not
to be in cloning or therapy but in drug discovery and toxicity testing. Among the
first researchers, paving a way for this trend, was Professor Lorenz Studer
from the Sloan-Kettering Institute in New York (8). His group demonstrated how
iPS cells could be used to produce cell models for rare diseases and to validate
the potency of candidate drugs.
However, in spite of a great deal of scepticism,
iPS cells are heading towards clinical trials in Japan (9). The Nobel Prize
will certainly give a tremendous boost to the Japanese teams working toward
this goal. The stakes are higher than ever before; it will almost be a question of national pride to make iPS cell-based therapy work
in the clinic. In any case, when these trials get underway, a new era for stem
cell research will begin.