Turning the clock back

October 10, 2012 01:11 am | Updated November 17, 2021 04:52 am IST

The Nobel Prize in Physiology or Medicine awarded on Monday to Sir John B. Gurdon of the Gurdon Institute in Cambridge and Dr. Shinya Yamanaka from Kyoto University for their path-breaking discoveries was not unexpected. Dr. Yamanaka had won two other prestigious science awards — the Albert Lasker Award in 2009 and the Wolf Prize in 2011. Winning the crowning glory of science awards just six years after publishing his landmark experiment shows how pathbreaking his work is. If Sir John laid the foundation in 1962 by showing that the nucleus of a matured intestinal frog cell inserted into a denucleated frog egg cell could develop into a normal tadpole, Dr. Yamanaka proved that inserting four critical genes into (differentiated) adult cells was sufficient to turn the clock back and make them behave like pluripotent stem cells. Much like the embryonic stem cells, induced pluripotent stem cells (iPSCs) are immature cells capable of becoming any of the over 200 specialised adult cells. The 2006 publication of his paradigm-shifting work on mouse skin cells, repeated in 2007 with human cells, shook the very foundation of developmental biology by demonstrating that cell specialisation is reversible. The publication of Dr. Yamanaka’s results, which helps to sidestep the ethical controversy surrounding embryonic stem cell research, could not have been better timed. It came about a month after George W. Bush, who was U.S. President at the time, vetoed a Bill seeking to enlarge federal funding for embryonic stem cell research.

Avoiding the ethical landmine is only a minor issue in the whole scheme of things. The real advantages will come from a wide gamut of applications. The most important and immediate application is using patient-derived iPSCs for studying disease mechanisms. Pharmaceutical companies have taken it to the next level by using stem cells, either embryonic or iPS cells, for screening drug candidates — for toxicity and potential new treatments. Several major drug companies have already jumped on the bandwagon of using them to screen drugs. After all, when it comes to drug discovery, human stem cells (embryonic and iPSC) are far superior to testing on animals. While scientists have found safer alternatives of introducing the genes into adult cells, certain critical issues pertaining to production and safety need to be resolved. The efficiency of turning adult cells into iPS cells is at present very low at about 1 per cent, and the great promise of using iPSCs for therapeutic purposes is still many years away. But according to Nature , it has not stopped the Japanese laureate from starting an ambitious project to produce by 2020 75 iPS cell lines for therapeutic use.

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