But there are other hurdles – some so challenging that many scientists have given up. For one thing, it seems, pushing stem cells in the right direction requires a unique touch and expertise. It’s not just anyone who can create egg and sperm cells in the lab, says Saitou.
Saitou and Hayashi, now at Kyushu University, lead teams that are world-renowned for their extraordinary skill. For example, their achievements might not have been possible without Hiroshi Ohta’s contribution. Ohta is an expert at anesthetizing newborn mice using ice, performing complex surgeries on them and injecting cells into their miniature gonads. The whole procedure must be completed within five minutes or the animal will die. Only a handful of people have such skills, which take months to develop. Saitou said: “I think our group is very lucky. “It was a gathering of many talented scientists.”
Work has been hampered by a lack of in-depth knowledge of how primitive forms of sperm and egg cells develop naturally in embryos — a process that is far from fully realized in humans. Some of the embryo’s cells begin to differentiate into these primitive sex cells at about 14 days. But in some countries it is illegal for researchers to even culture human embryos more than 14 days. Azim Surani, who is researching precursors of artificial sex cells at the University of Cambridge, UK, said: ‘They’ll put me in jail if I’m past 14.
From a research standpoint, the problem is that the 14-day rule “appears as soon as the embryo starts to get interesting,” says Surani. Unable to study the crucial process of how primitive cells begin to form egg and sperm cells, scientists are limited in their ability to mimic it in the lab.
Even if scientists can study embryos more freely, some mysteries will remain. Once the cells that make the egg and the sperm are made, they are kept in a suspended animation until puberty or ovulation. What happens to them in the middle years? And how important is this period for the health of the mature egg and sperm? “The honest answer is we don’t know,” Surani said.
Stem cells in the laboratory must also be generated and cared for under the correct conditions. To survive, they must be bathed in a cup of nutrients that must be replaced every day. “It takes a lot of time and effort… and a lot of money,” said Bjorn Heindryckx at Ghent University in Belgium, one of the scientists who gave up making human eggs this way in the lab. “The results were too limited compared to the effort and the money we spent on it,” he said.
Part of the challenge is that for progenitor stem cells to develop into fully mature egg or sperm cells, they must be placed in an environment that mimics a newly developed ovary or testicle. The mouse researchers used tissue taken from mouse embryos to induce stem cells to differentiate into sex cells. But similarly, using human tissue from discarded embryos is an ethical and legal issue. So scientists are working on how to create the right environment without using tissue from embryos.
As a result it will likely take a highly skilled team years of dedicated research. “It’s not impossible, but it won’t be easy,” Surani said.