The League of Extraordinary Biologists
In August 2006, shortly after Hochedlinger opened his new lab at MGH, a startling paper appeared. A Japanese scientist named Shinya Yamanaka believed he’d found the Holy Grail: a way to take adult cells and reprogram them into any other kind of cell whatsoever. The implications were huge. Up to that point, only embryonic stem cells were proven to have this prized malleability. Politically, though, the use of embryonic stem cells was problematic, decried by religious conservatives on pro-life grounds and, not coincidentally, subjected to a moratorium by the Bush White House. If Yamanaka was right, scientists would be able to skirt that minefield entirely.
Though now settled in at Harvard, Hochedlinger was still in close touch with Jaenisch. After reading Yamanaka’s paper, "I talked to my old boss," Hochedlinger says, "and he said, ‘Nay, this is bullshit.’" Yet as time went by, both men wondered, Could Yamanaka be right?
Out of loyalty, Hochedlinger had thus far focused his efforts on areas unrelated to Jaenisch’s. But they both sensed that Yamanaka’s work might pave the way for the biggest stem cell discovery yet. The Japanese researcher’s experiment had yielded cells that developed to a point somewhere between the adult skin cells he’d started with and the embryonic cells he wanted to end up with. While they showed the promise of transforming into any other cell—of possessing "pluripotency"—Yamanaka hadn’t been able to demonstrate anything beyond that.
Hochedlinger first asked his most gifted Ph.D. student, Nimet Maherali, to try to reproduce Yamanaka’s results. A few weeks later, Hochedlinger got an e-mail from her: She had succeeded. His eyes lit up. He realized he could greatly improve on what Yamanaka had done. He could take a skin cell and not just turn it into a fully pluripotent cell (also known as an induced pluripotent stem, or IPS, cell), but also coax that same cell to become any of the 220 mature tissue types that make up the human body—all without using a single embryonic cell.
Hochedlinger believed he could do this because the creation of IPS cells was directly related to the nuclear transfer work he had learned at MIT. But he was painfully aware that Jaenisch, as the godfather of nuclear transfer, had to be thinking just as he was, and in all likelihood working toward the same end. What’s more, if IPS cells succeeded it would democratize the field, allowing the reprogramming of cells through far easier techniques and ending Jaenisch’s long reign. Hochedlinger spent several sleepless nights before making his decision: The advancement he had in mind was too important not to directly challenge his mentor.
Both Hochedlinger and Jaenisch were careful to keep their research under wraps before publication. They knew what was at stake. As the 2006 holidays rolled around, they ordered their respective teams to drop everything to work on IPS cells. "Rudolf and Konrad became like the heavyweight prizefighter standing in against his protégé," Eggan says. "It’s pretty intense. I’m really glad not to be a part of it." Hochedlinger told the seven people in his Cambridge Street lab they would have to stay at it round the clock; one student brought in a sleeping bag.
On June 6, 2007, Hochedlinger published his findings in the academic journal Cell: Stem Cell. It was a momentous achievement. It was also one, it turned out, he’d have to share—that same day, Jaenisch and Yamanaka published their respective work on IPS cells in Nature. All had found separate ways to reach the same conclusion. As much as he’d wanted to stand alone, Hochedlinger was in part relieved. His mentor had adapted. And their discoveries had even more impact for having arrived together.
Jaenisch is fiercely competitive, but he glows when talking of Hochedlinger. To him, Hochedlinger is still the young man who sent a tentative e-mail from Austria 10 years ago. His accomplishments leave Jaenisch as proud as any father, even as Hochedlinger has become Frazier to his Ali. "It’s an interesting tension," Jaenisch says. "But I think there’s openness to try not to make this come into an unpleasant relation."