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Thursday, December 2, 2021

Conception: How Silicon Valley plans to turn blood into human eggs made in the laboratory

A few years ago, a young man from the California science and technology community began to appear in the world’s leading developmental biology laboratory. These laboratories are deciphering the secrets of embryos and are particularly interested in how eggs are formed. Some people think that if they find this formula, they can copy it and convert any cell into an egg.

Their visitor Matt Krisilov said he wanted to help. Krisiloff knows nothing about biology, he is only 26 years old. But after leading a research project at Y Combinator, a well-known startup incubator in San Francisco, he said that he was an early funder of companies such as Airbnb and Dropbox. Good connections” can reach wealthy technology investors.

Krisiloff is also particularly interested in artificial egg technology. He is gay, and he knows that in theory, a man’s cell can become an egg. If possible, two men can have a child with whom they are genetically related. “I am interested in the idea of’When can same-sex couples have children together?'” Krisiloff said. “I think this is a promising technology to achieve this goal.”

The company Krisiloff founded today is called concept, Is the largest commercial enterprise, pursuing the so-called in vitro gametogenesis, which refers to the conversion of adult cells into gametes-sperm or egg cells. It employs approximately 16 scientists and has raised $20 million from well-known technology figures including OpenAI CEO and former Y Combinator president Sam Altman; Jaan Tallinn, one of the founders of Skype; and Co-founder of Recursion Pharmaceuticals Blake Borgeson.

The company initially tried to make replacement eggs for women. This is scientifically easier than using male cells to make eggs, and it has a clear market. People have children in their later years, but women’s supply of healthy eggs drops sharply in their 30s. This is one of the main reasons for patients to visit IVF clinics.

Conception begins with the blood cells of a female donor and attempts to convert these cells into the first “proof-of-concept human egg” made in the laboratory. The company hasn’t done this yet—neither have others. There are still scientific problems to overcome, but Krisiloff sent an email to supporters earlier this year, stating that his startup may be “the first company in the world to achieve this goal in the near future.” It said that artificial eggs “may become one of the most important technologies of all time.”

Embryo manipulation concept

Nicholas Ortega

This is not an exaggeration. If scientists can produce a supply of eggs, it will break the rules of reproduction as we know it. Women without ovaries—for example, because of cancer or surgery—may have biologically related children. More importantly, the laboratory-made eggs will remove the age limit for women to give birth, allowing women to give birth to relevant babies at the age of 50, 60 or even longer.

The prospects for extracting egg cells from blood draws are far-reaching – and ethically challenging. Human fetal tissue is needed for the conception process to make eggs from stem cells. If reproduction is separated from the accepted facts of life, it may lead to unfamiliar situations. Not only does it open the door for same-sex reproduction, it may even open the door for one person-or four people-to give birth to offspring.

More realistically, because this technology can turn eggs into a man-made resource, it can add momentum to the design of children’s roads. If doctors can create a thousand eggs for a patient, they will also be able to fertilize all the eggs and conduct tests to find the best embryo to score their future health or intelligence. Such laboratory processes will also allow unrestricted gene editing using DNA engineering tools such as CRISPR. As Conception stated in a publicity issued earlier this year, the company expects artificial eggs to achieve “large-scale genome selection and editing in embryos.”

Krisiloff said: “If you can make a meaningful choice against the risks of Parkinson’s disease and Alzheimer’s disease, I think it will become very desirable.” The potential business and health rewards may be huge.

For scientific reasons, it is expected to be more difficult to turn a person’s cells into a healthy egg, and Conception has not even tried it. But this is also part of the company’s business plan. Perhaps when Krisiloff prepares to start a family, the two men will be able to make equal contributions to the genetic makeup of IVF embryos. Then, the surrogate mother can take the child to term. “I do think it is possible,” Krisiloff told MIT Technology Review. “When is this a question, not if.”

A mouse tail

The following is the working principle of egg making technology. The first step is to take a cell from an adult-say a white blood cell-and transform it into a powerful stem cell. This process relies on a Nobel Prize-winning discovery called reprogramming, which allows scientists to induce any cell to become a “pluripotent cell”-capable of forming any other type of tissue. The next step: coax the induced stem cells into eggs with genetic makeup that matches the patient.

The last part is the scientific challenge. Certain cell types are easy to make in the laboratory: After placing pluripotent stem cells in a petri dish for a few days, some cells will start beating spontaneously like heart muscle. Others will become fat cells. But eggs may be the most difficult cell to produce. It is huge-one of the largest cells in the body. Its biology is also unique. A woman is born full of her eggs and will never produce them again.

In 2016, two Japanese scientists Katsuhiko Hayashi and his mentor Mitinori Saitou took the lead in transforming mouse skin cells into completely in vitro fertilized eggs.them Report How did they start with trimmed cells, induce these cells to become stem cells, and then guide them halfway along the path to becoming an egg. Then, to accomplish this task, they hatched these primordial eggs with tissue collected from the ovaries of the mouse fetus. In fact, they had to build miniature ovaries.

“It’s not a question of’Oh, I can make eggs in a petri dish?’ David Albertini, an embryologist at the Bedford Research Foundation, said: “It’s a cell, it depends Because of its position in the body. “So it’s about creating an artificial structure that can review the process. “

uninvited guest

One year after the Japanese mouse breakthrough, Krisiloff began visiting the biological laboratory to see if the process can be repeated in humans. He appeared in Edinburgh, England, used Skype with Israeli professors, and made a pilgrimage to the center of Fukuoka Kyushu University Lin.

There, he met Pablo Hurtado González, a biologist who visited the laboratory on a scholarship, and he will join Krisiloff as the founder of Conception. The third co-founder Bianka Seres, an embryologist working in an IVF clinic, later joined the team.

Krisiloff graduated from the University of Chicago and previously served as the director of Y Combinator Research, where he initiated a project to study the provision of basic monthly income for people in the San Francisco area. Y Combinator is the most famous entrepreneurial school in the world. The idea of ​​its research project is to give away funds without attaching any conditions, as a strategy to prepare for future work to be replaced by automation.

The founder of Conception.bio
A startup company called Conception is trying to eliminate the age restriction on mothers by converting blood cells into human eggs. Its founders (from left) are Bianka Seres, Matt Krisiloff and Pablo Hurtado González.

Christopher Williams

Krisiloff said that after he started dating Altman, then Y Combinator president, he resigned from the role. Although this relationship did not last, the job change allowed him to work full-time in the new egg company and received initial investment from Ultraman. The company was originally called Ovid Research and changed its name to Conception this month.

Some researchers feel that these young entrepreneurs are already at a loss. The science of in vitro gametogenesis is dominated by a small group of university research groups who have been studying this issue for many years. “When I talked to them, they knew nothing, completely ignorant of how to start a project,” Albertini said. “They asked me what kind of equipment I wanted to buy. It was’How do you know you made an egg? What would it look like?'”

Another scientist Krisilov knew was Jeanne Loring, a stem cell biologist at the Scripps Research Institute. In collaboration with the San Diego Zoo, Loring had previously frozen one of the cells. The last northern white rhino, An endangered species. If she wants to resurrect this animal, she will be interested in egg-making techniques. “They are young, optimistic, and have money in their pockets, so they don’t rely on persuading others,” Lorraine said. “Sometimes, being naive is indeed a good idea.”

Krisilov is convinced that reproductive technology may be as attractive to technology investors as artificial intelligence or space rockets. As Barry Behr, a reproductive endocrinologist at Stanford University, said, “Now, if you write down’fertility’ on a piece of cardboard and take it to Sand Hill Road, you can get funding.”

The problem with artificial gametes is that medical products will not appear for many years-and there are complex responsibilities, such as who should be blamed if the final baby is abnormal. Krisiloff does not see these as obstacles to forming a company. In fact, he believes that more start-ups should try to solve “difficult” scientific problems and find that they can emerge faster in the business environment. “My argument is that if people turn research organizations into for-profit entities, there may be more funding,” he said. “I strongly believe in more basic research conducted in the context of the company.”

Fetal tissue

Krisiloff’s company has never issued a press release or sought public attention. That’s because his team has not yet produced human eggs, and he does not want to be seen as promoting biological “steam appliances.” Krisiloff said that Conception is still working hard to achieve its first technical benchmark-the production of human eggs and patented manufacturing methods.

This is also the goal of academic researchers like Japan who make mouse eggs. But repeating this breakthrough with human cells is daunting. Since the formula involves mimicking the natural steps of egg development, the duration of the experiment is almost as long as pregnancy. For mice born within 20 days, this is not a problem, but in humans, each experiment may take several months.

When I met Saitou and Hayashi in 2017, they told me that replicating mouse technology in humans is another disturbing difficulty. Complete repetition of this formula requires aborted tissue: scientists must obtain follicular cells from human embryos or fetuses that are several weeks old. The only option is to learn how to make these necessary support cells from stem cells. They predict that this in itself will require a lot of research work.

At Conception, scientists began to experiment with the fetal tissue method, which they believed was the fastest way to obtain a proof-of-concept egg.Krisilov put a lot of effort into obtaining this material-at one point even Tweet on abortion provider directly. He also sought cooperation with the University of California, Los Angeles and Stanford University, although these efforts were unsuccessful. He declined to say where Conception is currently receiving organizational donations.

Fetal tissue research is legal, but extremely sensitive, and for some members of the public, this is not just offensive. During Trump’s administration, health officials set up new obstacles, including arranging for those who oppose abortion to review funding. Krisiloff said the company still uses human fetal tissue, but now it is more commonly used to understand the molecular signals that characterize key cell types, so scientists can try to reconstruct these molecular signals from stem cells.

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