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 ofConception, 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 havealready 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
The company has released few details about its experiments and hasn't published its results in a scientific journal. Independent scientists haven't been able to validate the claims. Some are skeptical.
"I have reservations that Conception has indeed achieved a follicle," saysAmander Clark, who is working on IVG at the University of California, Los Angeles. Clark helped organize an Aprilworkshop at the National Academies of Sciences, Engineering, and Medicine in Washington, D.C., where Krisiloff described the company's work. "The conclusion was based on two biomarkers, one for the follicle cells and one for the oocyte. I would need to see more evidence than this," Clark says.
But others are inclined to believe the claims.
"Conception has a team of 30-plus scientists, as well as access to sufficient funding and resources to support rigorous IVG research," says Dr.Paula Amato of the Oregon Health & Science University in Portland, who participated in the workshop. "I wouldn't be surprised if they indeed had reached a primary follicle stage."
While that would be a "significant step forward," Amato adds: "Sharing their results in a peer-review publication could lend credibility to their claim and ensure that their data have undergone critical evaluation by experts in the field."
Krisiloff acknowledges that a lot more research is needed to prove the company's claim that its technology could produce viable eggs safely. But he says Conception eventually plans to publish the results, and he's confident they're on the cusp of success.
"The structural organization is very clear that they are follicles — beyond that, we did not show all data verifying as to what we have, but we have more markers indicating they are so," Krisiloff wrote later in an email. "We are confident these are follicles."
Conception is one of a handful of companies around the world that have started to develop IVG. A smaller startup called Ivy Natal in nearby San Francisco is using the gene-editing technique known as CRISPR to try to leapfrog Conception and make eggs and sperm from stem cells more quickly and safely.
"We've got a long ways to go, but it's an exciting time," Jeffrey Hsu, who co-founded Ivy Natal, says during an interview at his workspace the next day. "For these prospective parents, it would be huge. It would be a game changer."
This sudden influx of private funding is creating a lot of excitement, but also a lot of fears.
The rapid development of IVG raises ethical concerns
"This could take us into a kind of Gattaca world," saysMarcy Darnovsky, who runs the Center for Genetics and Society in Berkeley.
IVG could accelerate the rush toward all kinds of dystopian scenarios, including designer babies, Darnovsky says. "Combining IVG and genome editing and commercialization, you've really got kind of a toxic stew to create people who are supposedly biologically superior to others," she says. "We don't want to pave the road toward any kind of future that looks anything like that."
But the potential benefits of technology to create eggs and sperm from stem cells would be substantial for many people, others argue.
"I'm a fan of the IVG idea," saysHank Greely, a Stanford University bioethicist. "I think it offers the possibility for millions of couples who desperately want to have kids that are genetically half-one, half-the-other who can't do that now to have those children."
That said, Greely also worries about commercial pressures pushing IVG so quickly. "I live in Silicon Valley, where the motto is 'Move fast and break things.' Of course it worries me," Greely says. "Happily, the [Food and Drug Administration] does not want you to move fast and break things. And the FDA has a lot of power. I'm confident the FDA will use that power. Because we don't think babies are like iPhones."
Greely acknowledges that rogue scientists could misuse IVG in other countries. And lots of applications raise thorny questions, including using cells from children, elderly people and even dead people to make babies. Cells stolen from people, such as celebrities, could be used to make babies without their consent. Single individuals could even make babies with nothing but their own DNA.
"Why worry about these wild scenarios? Who in the world would do that?" Greely asks. "And then I think: There are 8 billion people in the world, and, you know, there are some rich megalomaniacs out there — we won't name names — who I can imagine might think that was cool."
Krisiloff and his colleagues acknowledge the concerns. But they stress they would make sure the technology is safe before proceeding. And they also say they would welcome government regulation.
"Can it go down pathways where, you know, people try to do weird, like, designer aspects or much more out-there things? Yeah, I mean, I think that's a fair thing to worry about and there's all sorts of gray areas that society really needs to figure out," Krisiloff says.
"But opening this door for so many more people is — including, you know, me and Pablo — a really cool thing. It could lead to so many people being able to have, you know, families and children to be able to have lives. I just think that's a really beautiful thing."
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