Scientists Are Figuring Out How To Grow Human Organs Inside Pigs


An international stem cell research team announced the creation
of the first human-pig embryos on Thursday, opening a new
frontier in research into “chimera” mashups of human and animal
tissues.

The study,
conducted by a team at the Salk Institute in California in
collaboration with researchers in Spain, is one of several
early attempts to grow human tissue inside of animals to
produce organs such as hearts and kidneys needed for
transplants.

“It’s important because we have been able to respond to a
question that the field was asking: Can human cells be mixed
with a large animal? The answer is yes,” team leader Juan
Carlos Izpisua Belmonte of the Salk Institute in San Diego,
told BuzzFeed News.

While labs have previously created human-animal chimeras, such
as mice transplanted with human cancer cells or immune systems
or even brain cells, these new experiments published in the
journal Cell are unique because they place human stem
cells — which can grow to become any of the different types of
cells in the human body — into animal embryos at their earliest
stages of life.

Implanted at such an early stage, animals born from such
chimeric embryos would possess a unique combination of human
and animal cells.

But the studies, which make the lines between human and animal
species murky, have already
ignited anxieties around potentially “humanizing” animals,
as well as stoking broader fears about tinkering with nature to
create life seen as unnatural.

In 2006, then-president George W. Bush called for making
human-animal chimera research — which he called “the most
egregious abuses of medical research” — punishable by a $1
million fine and up to 10 years in prison.
The bill never passed, but in 2015, the National Institutes
of Health
placed a ban on federal funding of any chimera research
using human stem cells, saying that the possibility the animals
could end up with human-like brains — and potentially,
human-like thoughts — was a strong enough reason to exercise
extreme caution.

Instead, Belmonte’s team was funded by private donors in the US
and Spain. They argue that their work is necessary, and that
any fears surrounding the products of their research, while
entirely understandable, are unwarranted. To address this, the
team killed the embryos early on, by four weeks of their
development.

“People worry about the germline and the brain — creating a
sentient animal,” Jun Wu, who led the study with Belmonte, told
BuzzFeed News. “But if we don’t allow the animal to be born,
then it’s just a mixture of human cells with the pig cells at
the early developmental stages. To us, that shouldn’t raise any
ethical concerns.”

“Not everything that we scientists can do should be done,”
Belmonte added.

Some bioethicists agreed. With 22 people a day in the US dying
while on waitlists for organs, Insoo Hyun, a bioethicist at
Case Western Reserve Medical School, told BuzzFeed News,
researching human-animal chimeras — however uncomfortable it
makes some — is crucial.

“The basic impetus behind this research is the sort of holy
grail of regenerative medicine— to help us replace our body
parts when they’re sick or diseased,” Amy Hinterberger, a
sociologist at the University of Warwick who specializes in
human-animal chimera research, told BuzzFeed News.

But, Hinterberger pointed out, mixtures of species have always
inspired fear in humans. Chimeras in Greek mythology were
monstrous lions with goat heads and snake tails. “To some
extent the figure of the chimera has always played an important
role in our cultural imaginaries about what’s natural, and
what’s not,” she said. “It’s something we still don’t know how
to grapple with.”

“Most of the labs around the world are trying to obtain
[organs] by growing cells in a petri dish,” Belmonte said.

Belmonte described how this type of research, pursued for more
than 10 years, has run into trouble since scientists aren’t yet
sure what makes stem cells differentiate into things like
organs or muscle cells or brain cells in the first place.
What’s more, growing cells on a flat plate makes it hard for
them to assemble into the three dimensional structures of
organs.

“So, we said, why don’t we let nature do the work for us?”
Belmonte said. “Why don’t we put human cells inside embryos?
They know very well what to do. We wanted to try to have human
stem cells not guided by us scientists, but by the embryonic
environment.”

Despite success creating rat-mouse chimeras (one lived two
years, setting a longevity record), doing the same experiment
in pigs using human stem cells was significantly harder for the
team. One reason was that pigs and humans are separated by 95
million years of evolution. Another was that human embryos have
a much longer gestation time than pigs, which are born after
just 114 days. Getting human stem cells to incorporate into the
pig embryo required tricky timing, which Belmonte likened to
merging onto freeway lanes moving at a very different speed
without crashing into oncoming traffic.

Once they successfully injected the pig embryos with the human
stem cells, the team implanted 41 female pigs with 30 to 50
chimeric embryos each. Only 18 pigs successfully got pregnant.
The scientists then extracted the embryos at three to four
weeks old, or one third of the way through the pig’s pregnancy,
to address concerns that any of the human cells would have
found their way into the developing pig embryo’s brain. Without
having an animal actually born, but still having all of the
organs of the embryo available for study, the scientists
avoided their main ethical hurdle — bringing what might be
considered a human-like pig into the world.

What they found was that the human stem cells had incorporated
into the pig embryo, mostly clustering in the muscle cells,
some organ precursors, and the spinal cord. They detected no
human cells in the brain. But the pig had very low levels of
human cell contribution overall — roughly one human cell per
100,000 pig cells — an efficiency problem they’ll need to
address if they want to use the pigs to create human organs
down the line.

“This is a small step, but it’s a very important proof of
principle,” Hyun said. “People were really hoping for
this.”

View this image ›

Juan Carlos Izpisua Belmonte
(left) and Jun Wu, who led the study. Joe
Belcovson

ID: 10403308

Belmonte and his group hope that in future experiments, they
will turn off certain organs’ development in the pig, which
would force the human cells to fill in the gaps to make fully
human transplantable organs.

“The prospect of growing a human organ may still be far away,
but there are other applications that are closer: modeling
human disease, drug screening, studying evolution, and
understanding early embryogenesis,” Belmonte said.

At the same time, they’re hoping to develop strategies to
ensure that the human cells don’t make their way into the pig’s
brain.

“Most people are concerned that if you mix too much human
material into the brain of a large animal, it may start having
conscious experiences that are more human-like. That’s so
hypothetical, we’re not anywhere close to that yet,” said Hyun.
“The bigger issue is the animal welfare question: what is the
well-being of the animal that’s gestating, the animals that you
use to get the embryos, and what’s the welfare of the thing
you’re going to birth live.”

Nevertheless, the researchers hope that the NIH might be
changing its tune on funding chimera research. Last August, the
agency
opened up to public comments on its policy regarding
human-animal chimera research. In November, 11 scientists
published a letter
criticizing the NIH for creating “a threat to progress” that
was based largely on unfounded fears. Meanwhile, the thorny
issues surrounding chimera research are still being weighed by
the agency, and the ban is still in effect.

“People are concerned about humanization — in relation to the
brain or reproductive capacities — but we’re not used to
talking about being human in such definitive ways,” said
Hinterberger. “For now at least, we don’t really have very good
metrics for human-ness.”



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