Four years ago, Kyoto University’s Shinya Yamanaka shocked the stem cell community when he announced at the annual meeting of the International Society for Stem Cell Research (ISSCR) that he had successfully reprogrammed skin cells to embryonic-like stem cells in mice. But, as he told delegates today at this year’s ISSCR meeting in San Francisco, he was in a foul mood at the time because many people in the audience were checking the scores of the Japan–Australia World Cup soccer match instead of listening to his talk. To add insult to injury, his home country of Japan lost the match 3-1.

In contrast, this year Yamanaka was delighted to report that Japan had just beaten Cameroon 1-0. Even better, his lab has discovered a new reprogramming recipe for creating safer induced pluripotent stem (iPS) cells, he told meeting attendees.

Yamanaka’s original reprogramming cocktail included four transcription factors: Oct4, Sox2, Klf4 and c-Myc. The last factor, however, turned out to be a double-edged sword: Adding c-Myc to the mix proved necessary to achieve reasonably efficient reprogramming rates, but the factor also led to higher rates of tumor formation in mice.

So, ever since the last World Cup, Yamanaka has been on the lookout for a substitute. Now, in a series of unpublished experiments he’s found a good candidate: L-Myc, a transcription factor closely related to c-Myc, but one that is not common in human cancers.

To prove the factor’s utility, Yamanaka borrowed the plasmid-based technique reported last year by University of Wisconsin-Madison’s James Thompson — a technique that allows cellular reprogramming without permanent modification of the genome. Yamanaka and his colleagues swapped c-Myc for L-Myc and added a plasmid encoding short hairpin RNA to knock down the p53 gene, which Yamanaka and others showed last year boosts reprogramming efficiency.

After only one electroporation to introduce the plasmids, Yamanaka’s team created bona fide human iPS cells from many different donors. Importantly, the introduced reprogramming genes were absent from the majority of these patient-specific iPS cell lines after a few weeks. In similar experiments in mice, Yamanaka showed that iPS cells induced with L-Myc led to chimeric animals with more than 80% of the cell lines contributing to the germline.

Together, Yamanaka’s results suggest that the highly problematic c-Myc might finally be dispensable, but only by replacing it with a similar — but safer — counterpart.