2020-03-01_Cosmos_Magazine

most vulnerable to the effects of drugs or maternal

infections that cause birth defects.

Given the gravity of these issues, you’d think an

avalanche of research would have shed light on them.

In fact, we know so little about the period it’s called

the ‘black box’ of embryology.

The implanted embryo, key to the enigma of early

life, is mostly invisible to science. The first reason

is structural: the embryo is sequestered in a uterus

beyond our gaze. The second is ethical: scientists

have grown human IVF embryos for 13 days in the

lab, but no one has gone beyond two weeks.

Endorsed by the UK’s Warnock Committee

in 1984 and then by the US National Institutes of

Health’s Human Embryo Research Panel in 1994,

the 14-day rule bans lab research on embryos beyond

that point.

It is around this time that a groove called the

primitive streak appears in the embryo: among other

things this marks a cut-off beyond which twinning is

impossible. This is the defining line of the individual

human which, some believe, is morally significant.

The 14-day rule is enforced by legislation in at least

12 countries.

The reasoning is clear, but the effect is to keep

the black box in shadow; science hasn’t had a way to

illuminate it.

NOW THE SPOTLIGHT FALLS on Fu’s plastic channels,

properly called microfluidic devices. In Fu’s earlier

experiments, only around 5-10% of his embryoids

reached that asymmetry waypost. But in his lab just

a short drive from the factory where Henry Ford

christened the first of his Model Ts, Fu has rewritten

the rules of embryoid production.

“With this microfluidic system, now we can

generate such human embryo-like structures with

very high efficiency, up to about 95%,” he says.

Fu’s system isn’t just meeting quality benchmarks,

and this is where the parallels with Motor City’s early

denizens become a little more pronounced. “It is a

scalable system,” he says. “I would even say that now...

it becomes a manufacturing system, depending on the

needs, right? Depending on how many you need.”

Fu’s tone is measured, matter of fact. But on this

moonshot to the dark side of our collective beginning

he carries the interests of Everyman, so be reassured

that he tells his tale with deep concern for our

wellbeing.

When he says the system “will be very useful for

high throughput screening”, that clinical parlance

describes the potentially vast benefits to real embryos

of testing hundreds of drugs on embryoids first. His

work could also show why so many pregnancies

miscarry – and improve our measly IVF success rate

of 20%.

been yet and, true to his engineering pedigree, he’s
done much of it by inventing a new 3D world for the
stem cell colonies to grow in.
“Most excitingly... in this first set of experiments,
is the fact that in a subset of those colonies we start to
see some asymmetric tissues, asymmetric embryonic
structures,” he tells me by phone.
Embryologists tend to get breathless about
symmetry, or lack of it. After natural conception,
when the sperm fuses with the egg to form the single-
celled zygote, there follows a cascade of dividing, with
new cells budding outwards in a uniform ball which,
at day three, becomes the 16-cell morula – Latin for
mulberry, which it resembles.
But around day six there is a major break from the
order of symmetry, as the front-to-back, belly-to-spine
axis appears. Anyone aiming to make a human embryo
needs to nail this. Fu didn’t just meet the milestone; he
also produced the cells that become the amniotic sac –
the fluid-filled bag in which the foetus floats.
“These asymmetric structures, basically they
resemble the core of the peri-implantation human
embryo,” he says.
Implantation. It strikes at the heart of this
project. Somewhere between six and 12 days after
conception, the human embryo nestles into the fleshy
wall of the uterus. This is essential if the pregnancy is
to continue. But when it goes wrong, it’s disastrous.
Nearly three quarters of all pregnancies that miscarry
by 20 weeks are a failure to implant. And the two
FROM TOP: JIANPING FU; GETTY IMAGES months after implantation are when the embryo is

THALIDOMIDE

One of the new wave of

sedative drugs introduced

through the 1950s, this

over-the-counter cure for

insomnia and morning

sickness was launched in

West Germany In 1956. In

Australia it was marketed as

Distaval or Tensival: “Safe

sedation and sounder sleep”.

By its withdrawal in 1961,

an estimated 2000 children

had died, with serious birth

defects identified in 10,000

more across 47 countries.

Thalidomide is now used to

alleviate conditions associated

with leprosy and HIV.

Fu’s stem cell chambers.

Gel channel

Cell cluster

formation

Induction channel

Cell loading

channel

Gel

pocket

Issue 86 COSMOS – 73

STEM CELL FRONTIER