alive in the lab for only 14 days for research purposes. After
that comes a crucial period when a few cells of the developing embryo—about 40—begin a mysterious trek toward what’s
called the gonadal ridge, the future ovaries or testicles. During
that journey, in ways still incompletely understood, the gametes gain the capacity to form a new being.
Reijo Pera has a personal interest in deconstructing how
that process works. Early in her career, she was diagnosed with
ovarian cancer, a rare kind called a granulosa cell tumor. The
disease left her infertile. “People said ‘Oh, it’s easy to adopt,
it’s easy to do this, that, or the other.’ And I became concerned
about a certain coarseness in health care about infertility,” she
says. She and her husband eventually decided to adopt a child
from Guatemala. By 2006, she was learning Spanish and telling Newsweek, in an item naming her that year as one of the 20
most influential women in America, that she was going to be
a mother. But then Guatemala ceased allowing foreign adoptions. By that time she was 49.
“So we just decided, we’ll make a life—me and you and a
dog named Boo. And that is what we did,” she says.
Despite giving up on motherhood, Reijo Pera did not let
the scientific question drop. Instead, she seized on what could
be the ultimate answer to infertility.
In 2006, a Japanese scientist named Shinya Yamanaka
reported that he’d hit on a formula for turning any adult cell,
including skin and blood cells, into what’s called an induced
pluripotent stem cell. These cells—iPS cells for short—had
undergone a kind of molecular amnesia. Just like cells found
in newly formed human embryos, they had no fixed identity
but were capable of becoming bone, fat, or any other part of
the body. The technique proved extraordinarily simple to use.
Some compared it the fall of a biological Berlin Wall.
Yamanaka was swiftly handed a Nobel Prize, just six years
later. With the development of iPS cells, he had solved an ethical controversy. He’d found a way to explore the earliest stages
of human development without using embryos discarded in
IVF. What’s more, iPS cells came from specific people. That
meant the resulting cells would be an exact match to a patient.
Scientists began talking about making supplies of “
personalized” neurons or heart cells for transplant procedures.
Reijo Pera was among those who understood that genetically identical stem cells could be especially important in
reproduction. How else to get a biologically related child
from a skin cell? Yet as straightforward as “rewinding” cells
with Yamanaka’s recipe quickly became, causing them to pursue a chosen fate has proved challenging. Scientists still don’t
know the exact combination of chemicals that prompt a cell
to develop into, say, a neuron rather than part of a toenail.
Figuring out that recipe—the precise set of ingredients and
steps needed to direct a cell’s development—has become one
of biology’s most daunting puzzles.
In June, 3,900 developmental biologists, biotech executives, and doctors converged at Boston’s cavernous convention center for the 15th annual meeting of the International
Society for Stem Cell Research. Yamanaka was there, trailed
by Japanese TV crews. Many of the scientists in attendance
work on creating specific cell types. One, Douglas Melton of
Harvard University, says he spent more than a decade determining how to turn stem cells into pancreas cells, the kind
that respond to insulin, and finally managed it in 2014. He
has two children with diabetes and hopes they could be cured
with a cell transplant. “We want complete dominion and
mastery over cell fate,” Melton told the convention crowd.
RECIPE FOR LIFE
During the meeting, I tracked down two Japanese scientists,
Mitinori Saitou and Katsuhiko Hayashi, who last November reported they had turned mouse tail cells into iPS cells
and then into eggs. It was a notable first—the first time in
the history of life that artificial eggs had been created outside
an animal. Using the synthetic eggs, they’d produced eight
mouse pups. Not only had those mice been healthy, but they
had gone on to reproduce. The discovery took more than five
years to perfect and 17 pages to describe in the journal Nature.
Yamanaka has called Saitou a “genius.”
The two scientists now aim to make human reproduc-
tive cells the same way. Saitou told me that Yamanaka him-
self directed him to try to master the production of human
gametes. “He asked me in person. He thought we should do it
because it’s scientifically very, very interesting,” he says. “We
are really interested in why these cells can make a new individ-
ual. It’s the ultimate way of controlling cell fate.”
Teams led by Yamanaka have been sweating to prove that
iPS cells will have practical applications: creating cures from
Japan’s Nobel Prize discovery has become a national priority.
In 2014, Japanese researchers carried out the first test of iPS-
generated cells, for treating blindness. But Saitou says artificial
gametes aren’t yet on the agenda. “It’s not low on the list—it’s
outside the list. It can’t even be compared to replacement cell
[therapy],” he says. “I think it’s very di;cult to use in vitro
germ cells to make humans. But not impossible.”
It’s not just technically di;cult: Saitou is nervous about the
ethical implications. He’s been deluged with letters from infer-
tile couples. Yet in Japan, research guidelines currently forbid
scientists from trying to use such cells to build an embryo. The
country’s cabinet is weighing whether to loosen the rules.