15 October 2012
Senior lecturer in stem cell science, King's College LondonAppeared in BioNews 677
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 laureate after, 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.