“Researchers Revive Abandoned Technique in Effort to Make Artificial Human Eggs in a Test Tube”, 2022-07-28 (; backlinks):
In a little-noticed study published earlier this year, scientists from Oregon Health & Science University reported the birth of 3 mouse pups that had been created with a never-before-used recipe for reproduction. Using a common cloning technique, researchers removed the genetic material from one female’s eggs and replaced them with nuclear DNA from the skin cells of another. Then with a novel chemical cocktail, they nudged the eggs to lose half their new sets of chromosomes and fertilized them with mouse sperm.
In a big step toward achieving in vitro gametogenesis—one of reproductive medicine’s more ambitious moonshots—the group led by pioneering fertility researcher Shoukrat Mitalipov now intends to use the same method to make artificial human embryos in a test tube.
If successful, the research holds enormous potential for treating infertility, preventing heritable diseases, and opening up the possibility for same-sex couples to have genetically related children.
“It’s one of those high-risk, high reward type of projects”, said Paula Amato, an OB-GYN and infertility specialist at OHSU who collects the human eggs used in Mitalipov’s experiments. “We have no idea yet if it will work, but age-related fertility decline remains an intractable problem in our field, so we’re eternally grateful to these private funders who are filling a real need here.”
…The group’s work on in vitro gametogenesis (IVG) in human cells is being made possible by an award from Open Philanthropy—a grant-making organization primarily funded by Facebook co-founder Dustin Moskovitz and his wife Cari Tuna—which will supply the researchers with $4 million over the next 3 years. The infusion of funds and the involvement of a scientist as storied as Mitalipov makes the ethical and legal questions surrounding mass egg and sperm production more urgent, experts told STAT.
In the U.S., there are no federal laws that prohibit this type of IVG work. However, Congress has barred any research that creates, destroys, or knowingly harms human embryos from receiving federal funding. At the state level, laws governing human embryo research vary widely with 11 states banning it entirely, 5 states expressly permitting it, and a lot of gray areas in between.
…So when a post-doc at OHSU named Eunju Kang proposed revisiting the idea of somatic cell nuclear transfer for IVG, Mitalipov was initially skeptical. But data from her initial mouse experiments proved persuasive. Mitalipov threw his support behind the project, and teamed up with a group at Weill Cornell Medicine in New York, including reproductive endocrinologist Gianpiero Palermo, who had successfully generated artificial human oocytes using cloning technology back in 2002. They published the results of their mice experiments in Nature Communications Biology in January. The OHSU team is now adapting those methods to see if they can generate artificial human eggs with properly separated chromosomes. If successful, they plan to then fertilize those eggs with sperm and grow the resulting embryos in the lab for 5 or 6 days to see if they develop normally.
They are betting that this method, while older, will prove better than the induced pluripotent stem cell technologies currently being advanced by artificial egg-making start-up outfits like Conception, Ivy Natal and Gameto. That approach requires the cells to be cultured for months rather than days, which can lead to epigenetic programming errors and chromosomal instability. Mitalipov also believes that starting with natural eggs will make it easier to strip the donor DNA of its cellular memory and return it to the primitive state known as totipotency—a critical step in enabling the embryo to eventually develop all the specialized tissues that make up a human body.