Biology Now, 2e

Engineering Life ■ 61

Life, Rewritten

The JCVI is just one institution among a large

group of universities and companies pursuing

synthetic biology, a field that aims to design

and construct new biological entities with novel

and useful functions. Scientists are working

to create algae that digest trash and produce

energy, microbes that use light and water to

create hydrogen gas, and bacteria that produce

new kinds of antibiotics to treat infections. With

synthetic biology “we can harness what nature

has made, but repurpose it,” says James Collins,

a synthetic biologist at Boston University. “We

can reprogram organisms and endow them with

novel functions.” In addition to useful tools, the

pursuit of artificial life sheds light on the very

origins of life. “It’s going to be a big challenge to

create a totally synthetic cell,” says Collins, “but

it’s fundamentally intriguing to explore how life

may have arisen on the planet.”

To make their own cell, scientists are pushing

the boundaries of cell theory, one of the unify-

ing principles of biology. Cell theory has two

main parts: every living organism is composed

of one or more cells, and all cells living today

came from a preexisting cell. By trying to engi-

neer a cell in the laboratory, Venter, Gibson, and

others are challenging the second part of the

definition.

Starting Small

The JCVI’s first step toward a synthetic cell was

a small one. In 2003, Venter’s team flexed its

scientific muscles by synthesizing the 11-gene,

5,386-base-pair genome of phiX174, a virus that

infects bacteria. A virus is a small, infectious

agent that can replicate only inside a living cell.

Most viruses are little more than stripped-down

genetic material wrapped in proteins, yet these

pathogens attack and devastate organisms in

every kingdom of life, from bacteria to plants

and animals. Though the JCVI team success-

fully created a virus with a synthetic genome,

it was not considered the first synthetic life,

because scientists debate whether viruses are

alive. (For more on this debate, see “Viruses—

Living or Not?,” page 66.)

Next, Venter and his colleagues moved up to

a bacterium, a living organism that consists of

a single cell. In 2010, they sequenced and built

the genome of a bacterium called Mycoplasma

mycoides (M. mycoides), an organism that can

cause the mammary glands of goats to swell.

They constructed the genome—a 1.1-million-

base-pair DNA sequence—using four neces-

sary ingredients: the nucleotides adenine (A),

thymine (T), guanine (G), and cytosine (C),

the building blocks of DNA. A, T, G, and C, orga-

nized in different combinations, carry all the

instructions for everything a cell does.

The team used a machine to read the nucle-

otide sequence of the M. mycoides genome and

then “print out” little bits of that code, creating

strands of DNA about 50–80 bases long. They

then strung these pieces together using living

cells as factories, inserting the short segments

into yeasts and Escherichia coli—small, single-

celled organisms. These organisms interpreted

the strands as broken pieces of DNA and

stitched them together, creating longer and

longer sequences. It was like building the Eiffel

Tower from a massive box of Legos, construct-

ing a single support beam at a time. The effort—

with many mistakes along the way—took years.

“It was very complex,” said Venter. “It was a long,

involved process.”

Congratulations, It’s a Cell

Once the DNA sequence of Mycoplasma mycoides

was complete and intact, it was up to the JCVI

team to transfer it into another species and make

it work. This was the experiment that almost

drove Gibson crazy. The researchers removed all

the DNA from a cell of a closely related bacte-

rium, Mycoplasma capricolum, and replaced it

with the M. mycoides synthetic DNA.

After months of trying, on that Monday morn-

ing at 5:00 a.m., Gibson cautiously scanned the

J. Craig Venter is an American biologist and founder

and CEO of the J. Craig Venter Institute. He led a team

to fully sequence and publish the human genome in

2001, and initiated the effort to create the first cell

constructed with synthetic DNA.

J. CRAIG VENTER