BERKELEY, CALIF. — On a cloudy day on a gritty side street near the shore of San Francisco Bay, a young man answers the door at a low concrete building.
“I’m Matt Krisiloff. Nice to meet you,” says one of the founders of Conception, a biotech startup that is trying to do something audacious: revolutionize the way humans reproduce. “So let me find them real quick,” says Krisiloff as he turns to look for his co-founders, Pablo Hurtado and Bianka Seres, so they can explain Conception’s mission.
“I personally think what we’re doing will probably change many aspects of society as we know it,” says Hurtado, the company’s chief scientific officer. “It’s really exciting to be working on a technology that can change the lives of millions of humans.”
Conception is trying to accelerate, and eventually commercialize, a field of biomedical research known as in vitro gametogenesis (IVG). “Basically, we’re trying to turn a type of stem cell called an induced pluripotent stem cell into a human egg,” Krisiloff says. “[This] really opens the door, if you can create eggs, to be able to help people have children that otherwise don’t have options right now.”
The experimental technology could help women who have lost their eggs to cancer treatment, women who have never been able to produce healthy eggs and women whose eggs are no longer viable because of their age.
IVG would enable these women to have their own genetically related babies at any age. That’s because induced pluripotent stem cells can be made from just a single cell from anyone’s skin or blood. So these lab-grown eggs would have that person’s DNA.
But the possibilities are even broader.
“My personal biggest interest in it is it could allow same-sex couples to be able to have biological children together as well,” Krisiloff says. “Yeah, I’m gay, and it’s something that got me so personally interested in this in the first place.”
Same goes for Hurtado. “There is something intrinsic about sharing a life that is half me and half my husband. I don’t have that capacity right now.” He adds, “I am devoting my life to trying to change that.”
IVG could create eggs from one of Hurtado’s cells that could then be fertilized with sperm from his partner. A surrogate mother could then carry the resulting embryo through to the birth of a baby genetically related to both men.
IVG could also create sperm for lesbian couples, allowing them to have babies with genes from both women. Transgender couples could also use IVG to have biologically related babies.
“How big of a deal it is for the world? I think it’s going to be pretty big,” says Seres, who has a background in in vitro fertilization. “And for individuals, I think it’s going to be life changing.” Japanese scientists have already successfully completed IVG in mice and are trying to translate their success to humans. Many other labs around the world are also racing toward the same goal.
But Krisiloff and his colleagues say their company has gotten closer to making IVG a reality than anyone else by creating structures found in ovaries known as follicles, which are crucial for maturing eggs.
“As far as we know, we’re the first in the world that have been able to do this,” says Krisiloff, who adds that the company has raised nearly $40 million and has expanded to a staff of more than 40. “So it’s really exciting.”
Mini-ovaries nurture immature eggs
Inside the company’s new laboratory, dozens of scientists wearing white lab coats are busy conducting experiments.
Hurtado starts by putting a sample of induced pluripotent stem cells that the company created from human blood cells under a microscope.
“They like to grow in what we call colonies,” Hurtado says. “So they don’t like to grow as individual cells. But they align with each other to be in these colonies.”
Under the microscope, the colonies look silvery blue, almost like crystals or clumps of snowflakes.
Next, Hurtado pulls a clear round dish out of an incubator. “These are primordial germ-cell-like cells,” he says. The company’s scientists created the primordial cells by exposing induced pluripotent stem cells to a special protein elixir. This ingredient coaxed them into developing into cells that could become either sperm or eggs. “They already decided that they are going to become an egg or a sperm, but they haven’t decided yet that they are going to become an egg, and that’s something we do later on,” Hurtado says.
He slides the dish under the microscope. Instead of clumping together in colonies, each primordial cell is more visibly distinct. “So in this case, they are much bigger. You can see each individual cell as a circle,” he says.
That’s because as these cells mature, each one becomes more independent, Seres says. “And in fact — fun fact is — egg cells are truly independent,” Seres says. “And they actually will need to become one cell within a follicle.”
Hurtado quickly returns the cells to the incubator and pulls out a rectangular dish. “These are some of our mini-ovaries,” he says. “These are a few weeks old now.”
Mini-ovaries are combinations of cells that the company has grown to nurture those primordial cells into becoming immature human eggs.
Another microscope projects an image of what’s in that dish onto a screen. “Hopefully what you can appreciate here is you can see our mini-ovaries. And then you can see a lot of dots that are really red fluorescent,” Hurtado says. “I like to call it a Christmas tree because it’s like all the lights — makes people happy when they see something like this.”
Just then, Seres and two of their colleagues who’ve been watching over our shoulders start to whisper excitedly. “People around here are quite happy with the result,” Hurtado says, laughing.
“It’s just nice to see them growing and doing very well,” says Alyssa Miller, one of the other scientists on the team. “We have two different methods for culturing them right now: kind of in a big ball and … so Pablo is telling me not to say anything more,” she says, her voice trailing off.
Hurtado had motioned for Miller to say nothing more because the company doesn’t want to disclose exactly how it managed to create the human ovarian follicles inside its mini-ovaries. “There are lots of parts of our research we cannot share right now,” Hurtado says. “We are still working on them.”
Finally, Hurtado, Seres and Krisiloff head back out of the lab to find some magnified images of some of the follicles. “The red dots I was showing you in the lab? At some point, they start becoming bigger and bigger and bigger,” Hurtado says. “So you can see those there. Those are quite big. And then you can see around — like a hollow — around each of those dots. Like a circle around. Those are actually the follicles.”
Within a year, Krisiloff and his colleagues hope, they’ll prove that the follicles in the mini-ovaries can develop the immature eggs into ones capable of being fertilized to make embryos and babies.
“We think it means we’re quite close to being able to have proof-of-concept human eggs — instead of this abstract idea that’s really just an imaginative science fiction idea — that really indicates that, ‘Hey, this technology is actually closer than people think,'” Krisiloff says.
Claims of progress but scant evidence…
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