Conception: How Silicon Valley Created a Plan to Turn Blood into Laboratory Eggs

A few years ago, a young man from the California tech scene began appearing in the world’s leading laboratories of developmental biology. These labs were deciphering the secrets of embryos and had a special interest in finding out how eggs are formed. Some thought that if they found this recipe they would copy it and transmute it into any cell in an egg.

Their visitor, Matt Krisiloff, said he wanted to help. Krisiloff knew no biology, and was only 26 years old. But after directing a research program at Y Combinator, the famous startup incubator in San Francisco, which was the first funding for companies like Airbnb and Dropbox, he said it was “well connected,” with access to tech-rich investors.

Krisiloff also had a specific interest in artificial egg technology. He’s gay, and he knew in theory that a man’s cell could turn into an egg. If that were ever possible, both men could have a child who was genetically related to both of them. “When can same-sex couples have children together?” says Krisiloff. “I thought that was the hopeful technology for doing that.”

Today Krisiloff started the business, call it Conception, is the largest commercial project seeking in vitro gametogenesis, which refers to the transformation of adult cells into gametes: sperm or egg cells. It employs about 16 scientists and has raised $ 20 million from well-known technology figures from Sam Altman, CEO of OpenAI and former president of Y Combinator; Jaan Tallinn, one of the founders of Skype; and Blake Borgeson, co-founder of Recursion Pharmaceuticals.

The company is initially trying to make replacement eggs for women. This is scientifically easier than laying eggs, and has a noticeable market. People are having children later, but a woman’s supply of healthy eggs is dropping by the age of 30. This is the main reason why patients visit IVF clinics.

The conception begins with the blood cells of female donors and these are trying to become the first “human egg of proof of concept” made in the laboratory. The company hasn’t done it yet, nor has anyone else. They are yet to overcome the scientific puzzles, but Krisiloff sent an e-mail to supporters earlier this year saying his startup could be “the first in the world to meet that goal in the not-too-distant future.” He says artificial eggs “can become one of the most important technologies ever created”.

That’s not an exaggeration. Scientists can create egg supplies that would break the rules of reproduction that we know. Women without ovaries — for example, due to cancer or surgery — may have biologically related children. What’s more, eggs made in the lab would break the age limits for female fertility, with women being able to have babies related to 50, 60 years or even older.

It is a profound and ethically fulfilling potential for egg cells to come out of the bloodstream. The process of conception required the tissue of the human fetus to lay eggs from the stem cells. And if reproduction differs from those that have been accepted in life events, unfamiliar scenarios could arise. It opens the door not only for same-sex reproduction, but perhaps for an individual — or even for four — to give birth to a cub.

More realistically, as technology can turn eggs into a manufactured resource, designers can overload the path for children. If doctors have laid a thousand eggs for a patient, they will also be able to test them to fertilize them and find the best embryos that can be obtained. scoring their genes for future health or intelligence. This laboratory process would also allow for unlimited genetic editing with DNA engineering tools such as CRISPR. Conception said in a field sent earlier this year that the company predicts that artificial eggs could allow for “large-scale selection and genomic editing in embryos”.

Krisiloff says, “If you were to make a significant choice against the risk of Parkinson’s, the risk of Alzheimer’s, I think that’s very desirable.” Commercial potential and health rewards can be high.

For scientific reasons, it is expected that it will be more difficult for a man’s cell to become a healthy egg, and Conception has yet to even test it. But it’s also part of the company’s business plan. Perhaps by the time Krisiloff is ready to start a family, the two men will be able to contribute equally to the genetic composition of an IVF embryo. A surrogate mother can then carry the baby in the middle. “I think it’s going to be possible,” Krisiloff told the MIT Technology Review. “When is the account, if not.”

Mouse tail

Here’s how egg-making technology can work. The first step is to take an adult cell — such as a white blood cell — and turn it into a strong stem cell. This process is based on a Nobel Prize-winning discovery called reprogramming, which allows scientists to turn any cell into a “pluripotent” one capable of forming any other type of tissue. Next step: These induced stem cells become the egg that matches the genetic composition of the patient.

The last part is a scientific challenge. Some cell types are very easy to make in the lab: leave the pluripotent am cells in a dish for a few days, and some will start beating naturally like heart muscles. Others will become fat cells. But an egg can be the hardest cell to produce. It’s huge, one of the largest cells in the body. And his biology is also unique. A woman is born with her whole egg and does no more.

In 2016, a pair of Japanese scientists, Kashuhiko Hayashi and his mentor Mitinori Saitou, were the first to turn mouse skin cells into fertile eggs, completely out of the body. They reported how, starting from the cells cut off in the tail, these were induced in the stem cells, and then directed along the path to become an egg. Then, to complete the work, these proto-eggs were incubated with tissue collected from the ovaries of fetal mice. In fact, they had to build small ovaries.

“It’s not a question of ‘Oh, can I make an egg in a petri dish?’ It is a cell that depends on its place in the body, ”says embryologist David Albertini of the Bedford Research Foundation.“ So it’s about creating an artificial structure that can restore the process. ”

Unexpected visitor

A year after the mouse breakthrough in Japan, Krisiloff began visiting biology laboratories to find out if the process could be repeated in humans. He appeared in Edinburgh in the UK, made Skype with Israeli teachers and also made a pilgrimage to Hayashi’s center at Kyushu University in Fukuoka.

There he met Pablo Hurtado González, a biologist who visited the laboratory through a grant, who would join Krisiloff as the founder of Conception. A third founder, Bianka Seres, an embryologist who worked at an IVF clinic, later joined the team.

Krisiloff, a graduate of the University of Chicago, was until then director of Y Combinator Research, where he launched a project to study the provision of basic monthly income to people around San Francisco. Y Combinator is the world’s most famous startup academy. His idea research project it was the gift of money without a chain as a strategy to prepare jobs for the future that automation takes.

CHRISTOPHER WILLIAMS

Krisiloff says he resigned from the post as Altman, who was president of the Y Combinator at the time. Although the relationship did not last, the job change freed him from working full-time at the fledgling egg company, with an initial investment from Altman. The company was originally called Ovid Research and changed its name to Conception this month.

Some researchers noticed that the young activists were obsessed. The science of in vitro gametogenesis has been dominated by a small group of university researchers who have been working on the problem for years. “When I talked to them, they had no clue, no clue, how to start a project,” Albertini says. “They asked me what equipment I needed to buy. ‘How would you know if you were making an egg? What would it be like? ‘”

Another scientist Krisiloff met was Jeanne Loring, a stem cell biologist at the Scripps Research Institute. Working with the San Diego Zoo, Loring had previously frozen cells in one of them the last northern white rhinos, an endangered species. He was interested in egg-laying technology if he was to resurrect an animal. “They’re young and optimistic and have money in their pockets, so they’re not dependent on convincing people,” Loring says. “Sometimes it’s a good idea to be naive.”

What Krisiloff knew for sure was that reproductive technology could be as attractive to technology investors as AI or space rockets. As reproductive endocrinologist Barry Behr of Stanford University puts it: “If you write ‘fertility’ on a piece of cardboard today and take it to Sand Hill Road, you can get funding.”

The problem with artificial gametes is that for many years there will be no medical products, and there are complex responsibilities, such as who is to blame if a baby is definitely not normal. Krisiloff did not see them as an obstacle to organizing a business. In fact, he believes that more startups should try to solve “hard” science problems and that discoveries can happen faster in a commercial setting. “My argument is that there can be a lot more funding if people turn research organizations into non-profit entities,” he says. “I have a strong belief in basic research that is done in the context of the company.”

Fetal tissue

The Krisiloff company has never released a press release or sought public attention. That’s because his team hasn’t made any human eggs yet, and he doesn’t want to see them promote biological “steam-ware”. Conception, Krisiloff says, is still trying to get its first technical reference, which is to produce the human egg and a patented process for making them.

That’s also the goal of Japanese academic researchers who made mouse eggs. But repeating the breakthrough with human cells is tremendous. Because the recipe mimics the natural steps that eggs develop, experiments can last as long as a pregnancy. This is not such a problem for mice born at 20 days, but in humans each experiment can take months.

When I met Saitou and Hayashi in 2017, they told me that copying mouse technology in humans had another worrying difficulty. Repeating the recipe in detail would require abortion tissue: scientists would need to get follicle cells from human embryos or fetuses within a week. The only alternative would be to learn how to manufacture these necessary support cells from stem cells as well. This, in itself, would require a great deal of research effort, they announced.

At conception, scientists began testing the view of fetal tissue, believing it to be the fastest way to get a proof egg of the concept. Krisiloff made great efforts to obtain the material, even at one point tweeting to abortion providers directly. He also sought collaborations with UCLA and Stanford, although these efforts were unsuccessful. The concept now refuses to say where it gets tissue donations.

Fetal tissue research is legal but highly sensitive, and is reprehensible to some audiences. In the Trump administration, health officials threw new hurdles, including opposing abortion advocacy subsidies. Krisiloff says the company still uses human fetal tissue, but it is now more widely used to understand molecular signals that are characteristic of key cell types, so scientists can try to recreate those that come from stem cells.