What started as an investigation into developmental mouse biology has become a lot more than that. Biologist Katsuhiko Hayashi discovered a way to turn mouse skin cells into sperm and egg cells — and actually used these modified cells to create a living baby mouse. The question is, can it work in humans?
Illustration via Nature
There is an absolutely terrific article about Hayashi's work by David Cyranoski over at Scientific American, exploring how his technique for creating germ line cells, or sperm and eggs, using novel methods developed by his senior colleague Mitinori Saitou at Kyoto University.
Many scientists try to create specific cell types in vitro by bombarding stem cells with signalling molecules and then picking through the resulting mixture of mature cells for the ones they want. But it is never clear by what process these cells are formed or how similar they are to the natural versions. Saitou's efforts to find out precisely what is needed to make germ cells, to get rid of superfluous signals and to note the exact timing of various molecules at work, impressed his colleagues. “There's a really beautiful hidden message in this work — that differentiation of cells [in vitro] is really not easy,” says Hanna. Harry Moore, a stem-cell biologist at the University of Sheffield, UK, regards the careful recapitulation of germ-cell development as “a triumph”.
Hyashi worked with Saitou to innovate new techniques that didn't require stem cells. This eventually led to that living mouse created from skin cells that had been turned into germ cells. The implications were staggering. Cells from a male mouse could be converted into eggs. Mice that were infertile could become fertile again, by turning their skin cells into viable germ cells. Other research groups have duplicated the team's results, though none have yet produced another viable baby.
When news of the research broke, the public went crazy. Not because they cared about mouse development, but because they hoped it could carry over into humans. It could mean new hope for infertile couples. And it might mean that gay couples could have children that are genetically related to two men, or two women.
Now, the team is focusing on humans. Cyranoski explains:
The group has already started tweaking human iPS cells using the same genes that Saitou pinpointed as being important in mouse germ-cell development, but both Saitou and Hayashi know that human signalling networks are different from those in mice. Moreover, whereas Saitou had 'countless' numbers of live mouse embryos to dissect, the team has no access to human embryos. Instead, the researchers receive 20 monkey embryos per week from a nearby primate facility, under a grant of ¥1.2 billion (US$12 million) over five years. If all goes well, Hayashi says, they could repeat the mouse work in monkeys within 5–10 years; with small tweaks, this method could then be used to produce human PGCs shortly after.
But making PGCs for infertility treatment will still be a huge jump, and many scientists — Saitou included — are urging caution. Both iPS and embryonic stem cells frequently pick up chromosomal abnormalities, genetic mutations and epigenetic irregularities during culture. “There could be potentially far-reaching, multi-generational consequences if something went wrong in a subtle way,” says Moore.
In other words, humans are a lot more complex than mice. And of course experimenting on them is a lot more ethically problematic. Still, it's a fascinating avenue of research. Read the whole article over at Scientific American.