But there are other obstacles, some so difficult that many scientists have given up. For one thing, moving stem cells in the right direction seems to require a unique touch and expertise. Not just anyone will be able to make eggs and sperm in the lab, Saitou says.
Saitou and Hayashi, now at Kyushu University, lead world-renowned teams with extraordinary skill. His achievements might not have been possible without the contributions of Hiroshi Ohta, for example. Ohta is an expert at anesthetizing newborn mice with ice, performing complex surgery on them, and injecting cells into the animals’ miniature gonads. The entire procedure must be completed within five minutes or the animals die. Only a few people have these skills, which take months to develop. “I think our group got lucky,” Saitou says. “It was a gathering of many talented scientists.”
The work is hampered by a lack of in-depth knowledge of how primitive egg and sperm forms develop naturally in the embryo, a process that is far from fully worked out in humans. Some of the cells in the embryo begin to differentiate into these primitive sex cells around 14 days. But in some countries, it’s illegal for researchers to even grow human embryos beyond 14 days. “They would send me to jail if I went beyond the 14th,” says Azim Surani, who works with artificial sex cell precursors at the University of Cambridge in the UK.
The problem, from a research standpoint, is that the 14-day rule “comes in right when the embryos start to get interesting,” says Surani. Unable to easily study the critical process of how primitive cells begin to form eggs and sperm, scientists have limited ability to mimic it in the laboratory.
Even if scientists could study embryos more freely, some mysteries would remain. Once the cells that make eggs and sperm are created, they remain in a sort of suspended animation until puberty or ovulation. What happens to them in the intervening years? And how important is this phase for the health of mature eggs and sperm? “The honest answer is we don’t know,” says Surani.
Stem cells in the laboratory must also be generated and cared for under precise conditions. To survive, they must bathe in a cocktail of nutrients that must be replaced every day. “It takes a lot of time and labor… and it takes a lot of money,” says Bjorn Heindryckx of Ghent University in Belgium, one of the scientists who has given up on creating human eggs this way in the lab. “The result was too limited for the effort and money we spent on it,” he says.
Part of the challenge is that for precursor stem cells to develop into fully mature eggs or sperm, they must be placed in an environment that mimics that of newly developing ovaries or testes. Researchers studying mice use tissue taken from mouse embryos to induce stem cells to differentiate into sex cells. But by the same token, using human tissue from rejected embryos is ethically and legally problematic. So scientists are working on ways to create the right environment without using tissue from the embryos.
The result is that it will likely require a highly skilled team of years of dedicated research. “It’s not impossible, but it wouldn’t be easy to do,” says Surani.