Now it’s hard to find a lab concentrating solely on embryonic cloning. Jamie Thomson, the first to pluck viable cells from a human embryo and grow them in culture, for instance, recently took charge of an institute focusing primarily on iPS cells. Although the technique is inefficient so far—less than 1 percent of cells become pluripotent—scientists see the iPS approach as a speedier path to cells suitable for disease research and, ultimately, the clinic.
With iPS, Wilmut enthuses, his team can study cell lines instead of wrestling to get them. “All you have to do is take some skin cells from somebody who apparently has inherited the disease, scatter some ‘magic dust’ on them and wait for three weeks,” he says. “And you’ve got pluripotent cells.” Wilmut and his collaborators, including George Daley of Children’s Hospital Boston and Chris Shaw of King’s College London, hope to use iPS cells to pinpoint mutations involved in ALS.
The method still does not promise quick cures. In ALS, for instance, researchers must speed up disease development and co-culture the various cells involved in the condition. Scientists would like to avoid retroviral vectors, risky because they deliver the genes randomly into the chromosome. Moreover, the new genes might vary in activity level, turn on in surprising ways or negatively influence other genes. Some teams succeeded in making iPS cells without the tumor-producing gene that Yamanaka used, but they also found that, as a result, they ended up with many fewer iPS cells.
Scientists do not fully understand how iPS reprogramming works—the inserted genes might represent a core regulatory circuit, or they might activate other genes. It is also not clear whether the results subtly differ from embryonic stem cells. No one yet has grown the two and made a side-by-side comparison, and survival after transplantation remains an unknown for both.
The iPS cells may force biologists to throw out accepted ideas about what it means to be a differentiated cell, says Zwaka, whose lab is studying characteristics of embryonic stem cells. Perhaps, he suggests, it is not necessary to take an embryonic cell through every step of development to create a particular cell type. There may be a set of “master regulators” that would enable, say, a skin cell to become an adult neuron without passing through the embryonic state.
Despite leaping on the iPS bandwagon, Wilmut and other cloning pioneers insist that embryonic stem cell research should continue. SCNT has offered important lessons about basic biology and will continue to enable studies of cell programming and reprogramming outside the genome. Only embryonic cells can answer questions about fertility and very early human development. Scientists will also likely rely on SCNT to produce mammalian models of diseases such as cystic fibrosis and for agricultural applications such as producing human proteins in animal milk.
“It’s simply too early to start putting one avenue over another,” says Daley, who is also president of the International Society for Stem Cell Research. His lab is using both SCNT and iPS to understand pluripotency. Daley fears that public sentiment may turn against embryonic work and dash hopes that a new U.S. administration will open up opportunities to clone new cell lines for research.
Indeed, as scientists turn their attention elsewhere, opponents of embryonic cell research have seized on the moment to attack. “There is no valid reason for any human cloning” or embryo destruction, wrote Tony Perkins of the Family Research Council. It is hard to escape the sense that SCNT research is on the wane. The ethical barriers and short egg supply remain daunting. If iPS pans out, Wilmut predicts, nuclear transfer to produce cell lines may one day become a history lesson.
Note: This story was originally printed with the title, "No More Cloning Around".