156 ■ CHAPTER 09 What Genes Are
GENETICS
P
igs,” thought Marc Güell. “What if we
could modify pigs?”
Güell, a young biochemist at Harvard
Medical School in Massachusetts, had been work-
ing with colleagues on techniques to manipulate
DNA (deoxyribonucleic acid), the genetic code
of life. In 2012, Güell and his colleague Luhan
Ya ng, a long w it h t heir boss, t he genet icist G eorge
Church, had begun adding and deleting genes
from organisms, a process known as genome
editing, using a new technological breakthrough
called CRISPR-Cas9—CRISPR for short.
Before the discovery of CRISPR (pronounced
“crisper”), editing DNA was difficult and expen-
sive, and it was typically done only in model
organisms such as mice and fruit flies—species
for which biologists had developed a solid tool
kit for genetic manipulation. CRISPR-Cas9, asimple but creative combination of a specific
protein and two single-stranded RNA (ribo-
nucleic acid) molecules, made genome edit-
ing inexpensive and available to all, not just
to well-funded genetics labs. It also enabled
researchers to quickly and efficiently change
the DNA of nearly any organism—like a “molec-
ular scalpel,” as one of the CRISPR inventors
called it—making it possible to edit genes in
fungi, plants, humans, you name it. “It was
the biggest change in my career,” says Güell.
“With CRISPR, everything is easier, faster, and
cheaper.”
CRISPR also provided the new opportu-
nity to edit more than one gene at a time, and
the team picked a unique initial specimen:
Sus scrofa domesticus, the domestic pig. “We
started to think about what would be a good
application to use this technology,” says Güell.
“One of the things that seemed like a very inter-
esting, very difficult problem was the lack of
organs for transplantation. We thought, what if
we could modify pigs to make them compatible
enough to be an unlimited source of organs?”
(Figure 9.1).Deep in the DNA
Each day in the United States, an average of
22 people die waiting for an organ transplant,
and 119,000 men, women, and children are
currently on the national transplant waiting
list, each hoping their name is called before it’s
too late.
Researchers have explored many ways to
grow and store organs for transplantation—from
freezing them to building them from scratch—
but one of the most promising, if you can look
past the mud and flies, is pigs. Our porcine
friends have long been considered an excellent
potential source of organs because their organs
are relatively close in
size to human organs—
including the heart,
liver, and kidneys—
and because pigs and
humans have simi-
lar organ anatomies
(Figure 9.2). In addi-
tion, pigs are an easier
sell to the public: inFigure 9.1
Experimental pig-to-baboon lung transplant
A lung from a pig engineered by CRISPR to prevent rejection is tested for
safety and efficacy in primates by being transplanted into a baboon.
“
Marc Güell (right) is a research fellow at the Wyss
Institute at Harvard Medical School, where he has
been working to engineer the pig genome for human
compatibility. He works in the lab of geneticist
George Church (left), a pioneer in genome engineering
and synthetic biology.MARC GÜELL AND GEORGE CHURCH