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science 2008-2009: 8: stem cells

By Jon E Agar, on 27 September 2009

Stem cells have the potential of turning into any other kind of cell in the body. It is this general-purpose nature that makes them such an extraordinarily attractive object to medical scientists developing new therapies and new tests.

But until 2007, human stem cells were very hard – physically and politically – to isolate, culture, manipulate and use. Previously, the only source of stems cells was the embryo. In 1981, embryonic stem cells had been isolated in the mouse. It took seventeen years before human embryonic stem cells were found. The difficulty was not just finding the tiny cells but also discovering the methods needed to grow and culture them, that is to say to turn stem cells into stem cell-lines. 

The techniques were immediately controversial, especially, given the embryonic source of the cells, within the worldwide catholic church and the conservative, “Pro-Life”, anti-abortion movement in the United States. President George W. Bush banned the use of federal funds to pursue research on any other than stem-cell lines derived before the 9th of August, 2001. In Germany, church leaders, such as Roman Catholic Cardinal Karl Lehmann, Green politicians, and a legacy of law written in the wake of Nazi atrocities, and intense debate over two years led to a similar restriction of researchers to work only on old stem-cell lines. Only the strong support of Chancellor Gerhard Schroeder and the minister for research, Edelgard Bulmahn, secured the continuation of limited imports of stem-cell lines into Germany. Schroeder and Bulmahn argued that if Germany did not do some stem cell research then it would be done elsewhere, with no ethical restrictions and to others’ economic gain.  

Indeed, embryonic stem-cell research did indeed flourish in areas of the world with less restrictions: Japan, Britain, and the individual states, such as California ($3 billion), Massachusetts ($1 billion) and Wisconsin ($750 million), in the United States that have made up the federal short-fall in funding. (Some states, such as Louisiana and North Dakota, criminalised such science; others, such as New Jersey, found that an attempt to fund research was rejected at the polls.)

This savage pulling of research in two directions – on one hand towards visions of making the blind see and the crippled walk again, and on the other towards criminalisation and dogmatic abhorrence – explains why the announcement of a new, non-embryonic source of stem cells was met with such enthusiasm. In 2006, at Kyoto University, Shinya Yamanaka had taken ordinary mouse cells and by making four, relatively simple genetic changes had caused some of them to revert to stem cell status. Within the year, working with his postdoc student Kazutoshi Takahashi in secrecy, Yamanaka had achieved the same with human cells. (He used viral vectors to introduce clones of four genes – Oct3/4, Sox2, c-Myc and Klf4 – to the human cells.) Yamanaka published his results on what he called induced pluripotent stem (iPS) cells in November 2007. Remarkably, on the same day, a Wisconsin pioneer of stem cell methods, James Thomson of the Univesity of Wisconsin in Madison, one of the original discoverers of human embryonic stell cells, independently announced the same iPS technique.

iPS cells became a goldrush in 2008 and 2009. Universities, such as Harvard, Toronto and Kyoto speedily established new facilities; scientists switched research fields; Addgene, a Massachusetts company that sold Yamanaka’s four reprogramming vectors received 6,000 requests from 1,000 laboratories since the original announcement of the mouse technique. In Japan, where Kyoto University had delayed applying for patents, the simultaneous publication sparked a national debate on whether the nation was losing its scientific lead. Billions of yen were made available for iPS science, and a Japanese patent was rushed through the system by September 2008.

Nor does iPS cell reserach raise no ethical issues. iPS cells might be used to derive gametes from any source of cells (a celebrity’s hair?), or to clone humans (it has been done with mice) or might induce cancers rather than cures.

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