A few years ago, a young man from the California technology scene began popping up in the world’s leading developmental biology labs. These labs were deciphering fetal privacy and had a special interest in how eggs were made. Some thought that if they invented that recipe, they would be able to copy it and convert any cell into an egg.
Their visitor, Matt Crisiloff, says he wants to help. Crisiloff knew no biology, and was only 26 years old. But after leading a research activity at San Francisco’s famous startup Incubator Y Combinator, which was the initial funding of companies like Airbnb and Dropbox, he said he was “well connected,” with access to wealthy technology investors.
Crisilf also had a special interest in artificial-egg technology. He was gay, and he knew that theoretically, a human cell could turn into an egg. If it were ever possible, the two men could have a child who was genetically related to both. “When can ‘gay couples have children together?'” I was interested in the idea. “I thought it was promising technology to do that.”
Today, Crisilf has launched a company called Conception, the largest commercial venture called in vitro gametogenesis, which involves turning adult cells into gamete-sperm or egg cells. It hired about 16 scientists and raised 20 million from celebrities, including Sam Altman, CEO of OpenAI and former president of Y Combinator; Jan Tallinn, one of the founders of Skype; And Blake Borgeson, co-founder of Rickerson Pharmaceuticals.
The company is primarily trying to create replacement eggs for females. It is scientifically simpler than making eggs from male cells and has a clear market. Humans have babies later in life, but a woman’s supply of healthy eggs calls her nose in her 30s. This is a major reason patients visit IVF clinics.
Pregnancy begins with the blood cells of female donors and attempts are made to transform them into the first “proof-of-concept human eggs” made in the lab. The company hasn’t done it yet বা or anyone else has. There are still scientific puzzles to be overcome, but Crisiloff sent an email to supporters earlier this year saying his startup could be “the first in the world to achieve this goal in the very near future.” It says artificial eggs could “become one of the most important technologies ever created.”
This is not an exaggeration. If scientists could supply eggs, it would break the rules of reproduction as we know it. Women without ovaries – for example, due to cancer or surgery – may be able to conceive a biologically related child. What’s more, lab-made eggs repeal the age limit for female fertility, allowing women to give birth to offspring related to age 50, 60 or older.
The possibility of egg cells from a blood draw is profound and morally fulfilling. Human embryonic tissue is needed in the process of conception to produce eggs from stem cells. And if reproduction is detached from the recognized truth of life, unfamiliar situations can arise. This opens the door to procreation, not just for the same sex প্র perhaps for one person বা or for four.
More realistically, since technology can turn eggs into a productive asset, it can supercharge the path of designer children. If doctors can make a thousand eggs for a patient, they will also be able to fertilize them and test them to find the fetus with the best results by scoring their genes for future health or intelligence. Such a laboratory process would allow uninterrupted genetic editing with DNA engineering tools such as CRISPR. Concept put it on a pitch shipped earlier this year, with the company speculating that artificial eggs could “select and edit large-sized genomes in embryos.”
Crisilloff says: “If you could make a meaningful choice against Parkinson’s risk, Alzheimer’s risk, I think it would be very desirable.” The potential commercial and health delivery can be huge.
For scientific reasons, it is expected that it will be difficult to turn a human cell into a healthy egg, and Conception has not yet tried it. But it is also part of the company’s business plan. Maybe, when Crisiloff is ready to start a family, two male IVF will be able to contribute equally to the genetic makeup of the fetus. A surrogate mother can then take the child in term. “I think it will be possible,” Crisiloff told MIT Technology Review. “The question is, when is it, if not.”
A rat’s tail
Here’s how egg-making technology works. The first step is to take a cell from an adult — say, a white blood cell — and transform it into a strong stem cell. The process is based on a Nobel Prize-winning discovery called reprogramming, which allows scientists to persuade any cell to become a “pluripotent” – capable of forming any other type of tissue. Next step: Cajol to convert those induced stem cells into eggs whose genetic makeup will match the patient.
This is the last part which is the scientific challenge. Some cell types are very easy to make in the lab: leave the pluripotent stem cells on a plate for a few days, and some will spontaneously start beating like heart muscle. Others will become fat cells. But producing an egg can be the hardest cell. It is huge – one of the largest cells in the body. And its biology is also unique. A female is born with her complete complementary egg and never makes it again.
In 2016, a pair of Japanese scientists, Katsuhiko Hayashi and his mentor Mitinori Saitou, were the first to transform skin cells from rats into completely fertilized eggs outside the body. They reported how, starting from a tail cut to a cell, they induced them into stem cells, which they partially indicated on the way to the egg. Then, to finish the work, they incubate these proto-eggs along with the tissue collected from the ovaries of the rat embryos. Practically, they had to make mini ovaries.
“It doesn’t matter. ‘Oh, can I make eggs in a petri dish?’ It’s a cell that depends on its location in the body, “said David Albertini, an embryologist at the Bedford Research Foundation. “So it’s about creating an artificial structure that can restore the process.”
A year after the progress of rats in Japan, Crisilov began inspecting the biology lab to see if the process could be repeated in humans. He came to Edinburgh, UK, Skype with Israeli professors, and made a pilgrimage to the Hayashi Center for Fukuoka Kyushu University.
It was there that he met Pablo Hurtado Gonzalez, a biologist who visited the lab on a scholarship to join Crisiloff as the founder of Conception. A third co-founder, Bianca Ceres, an embryologist who worked at an IVF clinic, later joined the team.
Crisiloff, a graduate of the University of Chicago, was then director of Y Combinator Research, where he launched a project to study to give people in the San Francisco area an initial monthly income. Y Combinator is the most famous startup academy in the world. The idea of its research project was to pay without attaching any strings as a strategy to prepare for the future where jobs are taken through automation.
Crisilov says he resigned from the role after he started dating Altman, who was president of Y Combinator at the time. Although the relationship did not last long, the change of job set him free to work full-time in a new egg venture with Altman’s initial investment. The company was originally called Ovid Research and has been renamed Concept this month.
Some researchers felt that young entrepreneurs were on top of their heads. The science of in vitro gametogenesis is influenced by a small cadre of research groups at the university who have been working on the problem for years. “When I talked to them, they had no idea, absolutely no idea, how to start a project,” Albertini said. “They were asking me what kind of equipment to buy. It was ‘How do you know if you make eggs? What does it look like? ‘”
Another scientist, Crisiloff, learned that he was Jean Loring, a stem cell biologist at the Scripps Research Institute. Working with the San Diego Zoo, Loring previously froze cells from one of the last northern white rhinos on the verge of extinction. He was interested in egg-making technology if he ever wanted to resurrect the animal. “They’re young and optimistic and have money in their pockets, so they don’t rely on people to understand,” Loring said. “It’s a really good idea to be stupid sometimes.”
What Crisilov knew for sure was that reproductive technology could make the same kind of appeal to investors as an AI or space rocket. As Stanford University reproductive endocrinologist Barry Behr puts it, “Nowadays if you write ‘Fertility’ on a piece of cardboard and take it to Sand Hill Road, you can make money.”
The problem with artificial gametes is that they are not going to be a medical product for many years এবং and there are complex responsibilities, such as who will be responsible if a child is not normal. Crisilf did not see these as obstacles to organizing a company. In fact, he believes that more startups should try to solve “difficult” science problems and that discoveries can be accelerated in a commercial setting. “My argument is that there could be a lot more funding if people turned research institutes into profitable ones,” he says. “I’m a big believer in more basic research going on in the company’s context.”
Crisiloff’s company has never issued a press release or drawn public attention. Because his team hasn’t made human eggs yet, and he doesn’t want to be seen as a biological “steam pot” propagandist. Crisiloff says the concept is still trying to achieve its first technical standard – a patented process for making human eggs and making them.
It is also a target of academic researchers like Japan who make rat eggs. But the epoch-making repetition with human cells is terrifying. Since the recipe involves mimicking the natural steps of egg development, the tests can be as long-lasting as pregnancy. This is not a problem for rats born in 20 days, but in humans, each test can take several months.
When I met Saitu and Hayashi in 2017, they told me that copying mouse technology in humans presented another problematic problem. Abortion tissue is needed to repeat the exact recipe: Scientists need to get follicle cells from a few weeks old human embryos or embryos. Learning how to make these necessary support cells from stem cells would also be the only option. This, in itself, would require a significant research effort, they predicted.
During pregnancy, scientists began trying embryo-tissue methods, which they believed were the fastest way to get concept-proof eggs. Crisilov made a massive effort to get the material – even at one point Tweeting abortion providers He also sought direct cooperation with UCLA and Stanford, although these efforts did not end there. He declined to say where the concept currently receives tissue donations.
Embryo-tissue research is legal but highly sensitive, and to some people it is more than disgusting. During the Trump administration, health officials threw out new hurdles, including enrolling opponents of abortion to review grants. Crisilloff says the agency still uses human embryonic tissue, but now it is often used to understand molecular signals that identify the types of stem cells so that scientists can try to recreate them from stem cells.