But there are other hurdles—some so challenging that many scientists have given up. For one thing, nudging the stem cells in the right direction requires, it seems, a unique touch and expertise. Not just anyone will be able to make egg and sperm cells in the lab, says Saitou.
Saitou and Hayashi, now at Kyushu University, lead world-renowned teams of extraordinary skill. Their achievements might not have been possible without the contributions of Hiroshi Ohta, for example. Ohta is an expert in anesthetizing newborn mice using ice, performing intricate 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 such skills, which take months to develop. “I think our group was kind of lucky, says Saitou. “It was a get-together of many talented scientists.”
The work is hampered by the lack of in-depth knowledge about how the primitive forms of egg and sperm cells develop naturally in the embryo—a process that is far from fully worked out in humans. Some of the embryo’s cells begin to differentiate into these primitive sex cells at around 14 days. But in some countries, it is illegal for researchers to even grow human embryos beyond 14 days. “They would send me to jail if I went beyond day 14,” says Azim Surani, who is working with precursors to artificial sex cells at the University of Cambridge in the UK.
The problem, from a research point of view, is that the 14-day rule “comes in just as the embryos start to get interesting,” says Surani. Without being able to easily study the critical process of how primitive cells begin forming egg and sperm cells, scientists are limited in their ability to mimic it in the lab.
Even if scientists were able to study embryos more freely, some mysteries would remain. Once the cells that make eggs and sperm are created, they are held in a kind of suspended animation until puberty or ovulation. What happens to them in the years in between ? And how important is this phase for the health of mature eggs and sperm? “The honest answer is we don’t know,” says Surani.
The stem cells in the lab must also be generated and cared for under precise conditions. To survive, they must be bathed in a cocktail of nutrients that must be replaced every day. “It’s very time consuming and labor intensive … and it takes a lot of money,” says Bjorn Heindryckx at Ghent University in Belgium, one of the scientists who have given up on creating human eggs this way in the lab. “The outcome was too limited for the effort and the money that we spent on it,” he says.
Part of the challenge is that for the precursor stem cells to develop into fully matured egg or sperm cells, they must be placed in an environment mimicking that of newly developing ovaries or testes. Researchers studying mice use tissue taken from mouse embryos to induce the stem cells to differentiate into sex cells. But similarly using human tissue from discarded embryos is ethically and legally problematic. So scientists are working on ways to create the right environment without using tissue from embryos.
The upshot is that it will likely take a highly skilled team years of dedicated research. “It’s not impossible, but it would not be easy to do,” says Surani.