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19spring 2011
Synthetic Cells
 daniel lee ‘13
cell BiologY
The methods of isolating and ma-nipulating genes to understand their roles in the genome have 
improved tremendously since their in-
ception in the 1970’s. In recent years, 
the growing precision and speed of 
these methods have allowed geneti-
cists to develop and refine such tools as 
DNA fingerprinting, disease-resistant 
crops, and tests for heritable diseases. 
In May 2010, scientists at the J. Craig 
Venter Institute, a non-profit research 
organization, added to this array of 
scientific tools methods for synthesiz-
ing artificial, self-replicating genomes. 
The creation and transplantation 
of the first human designed genome was 
an immense technical achievement that 
took JCVI researchers 15 years and $40 
million to complete (1). The research is 
proof of principle that genomes can be 
digitally designed, and then inserted 
into cells, thereby enabling a great deal 
of cellular customization. Geneticists 
have heralded this feat as the beginning 
of a new wave of interest into synthetic 
cell research (2). While both scien-
tists and non-scientists have naturally 
raised bioethical concerns, government 
and commercial funding remain strong 
(1). JCVI’s synthesis and transplan-
tation of an artificial genome is a sig-
nificant landmark for modern genetics.
 
The Experiment
The purpose of the experiment 
was to transplant an artificially created 
genome of the bacteria Mycoplasma 
mycoides to a similar bacteria Myco-
plasma capricolum (3). It was hypoth-
esized that doing so would convert the 
M. capricolum cells into M. mycoides 
as JCVI laboratories had done in the 
past with a naturally created genome 
(4). The challenge in the experiment 
was in sequencing and synthesizing an 
artificial genome that could accurately 
mimic its non-synthetic counterpart. 
To begin, researchers sequenced 
the genome of M. mycoides into a com-
puter file (4). The researchers then ed-
ited the file, added new sequences, and 
sent it to Blue Heron, a bio-synthesis 
company. There, it was made into 1,078 
pieces, each 1080 base pairs long (4). 
Complementary base pair se-
quences at the ends of these snip-
pets allowed scientists to glue them 
together. Since connecting all these 
sequences at once would have been 
technically overwhelming, the pro-
cess was divided into three-stages, 
with each stage forming larger and 
larger pieces until the entire genome 
of M. mycoides was reconstructed (3). 
upon completion the sequence 
was introduced to M. capricolum pop-
ulations (4). The result was a group of 
cells that expressed the characteristics 
of a wild-type M. mycoides using the cel-
lular machinery of M. caprciolum (4).
 
Relevance to Science
The technical significance of this 
feat is substantial. This process required 
not only precise synthesis, but also care-
ful sequencing of the natural M. my-
coides genome. Several times through-
out the study, slight errors stalled the 
entire effort. In one instance, a single 
base pair miscalculation took research-
ers three months to find and fix (5). 
Throughout the process of recon-
structing the genome, JCVI developed 
new techniques and refined existing 
ones to adapt to the unprecendented 
variety required of a synthesis that size 
(3). The effectiveness of JCVI’s refined 
methods has encouraged additional re-
search into genome synthesis. By being 
able to selectively put together a rep-
licating genome, populations of cells 
can be tailored to have advantageous 
functions such as attacking water-born 
pathogens (5). The biotech company 
Synthetic Genomics Inc., owned by J. 
Craig Venter, is already working on ap-
plying the techniques developed from 
this work for commercial use (5). The 
company has a $600 million contract 
Image courtesy of Tom Deerinck and Mark Ellisman of the National Center for Microscopy and Imaging Research at the University of California at San Diego.
A scanning electron micrograph of Mycoplasma mycoides JCVI-syn1.0: The J. Craig Venter 
Institute’s “synthetic cell.” 
 Dartmouth unDergraDuate Journal of science20
with Exxon Mobil to build a breed of al-
gae that can capture carbon dioxide and 
turn it into clean-burning fuel (5). Three 
other biotech companies, Amyrise Bio-
technologies, LS9, and Joule unlim-
ited, are working on similar projects 
to create fuel cells which are funded 
by the Department of Defense (1). 
Synthetic cells are also being de-
veloped for other uses. JCVI is current-
ly working on making its findings more 
accessible for other scientists to modify 
for their specific research needs. Dr. 
Daniel Gibson, who led the synthetic 
genome project, said that the JCVI 
research team is now trying to build a 
genome with only the minimal compo-
nents needed to sustain a living cell (6). 
Doing so, Gibson claims, will allow sci-
entists to have a generalized set of fun-
damental pieces needed to construct 
a working cell, providing a base for 
other labs to build on in the future (6).
The Future of Genome 
Synthesis
The ability to construct genomes 
initially concerned many bioethicists. 
Following the publication of JCVI’s 
research, President Obama requested 
that the White House bioethics com-
mittee investigate JCVI’s finding 
(2). It was feared that JCVI’s efforts 
would give way to new research work-
ing to synthesize life from non-living 
components, a bioethical taboo (2).
However, the committee ruled 
otherwise soon after the investiga-
tion was commissioned. David Balti-
more, a geneticist at Caltech closely 
involved with the investigation, told 
the New York Times that while JCVI’s 
research is a “technical tour de force…
[the research] has not created life, only 
mimicked it” (2). The cellular machin-
ery used to hold and express the syn-
thetic genome was created by natural 
means. Additionally, the genome itself 
was built off the blueprint of an exist-
ing organism, not an original creation. 
The JCVI website states, “We 
do not consider [our research] to 
be ‘creating life from scratch’ but 
rather we are creating new life 
out of already existing life.” (6). 
Whether biologists will ever be 
capable of creating an original life 
form is unlikely. Not only would ethics 
Image courtesy of the J. Craig Venter Institute.
The JCVI Synthetic Biology Team, including Dr. Daniel Gibson (back row, second from right), leader 
of the synthetic genome project.
committees quickly terminate such re-
search efforts, the technical and finan-
cial effort to produce such an organism 
would be impractical. Naturally occur-
ring organelles and other cellular com-
ponents are already being effectively 
harnessed, and the need for modified 
ones is not pressing. Moreover, even 
if such components are developed, the 
level of coordination that they would 
need with one another would be an 
even more daunting and costly effort. 
The focus of JCVI’s research on 
the software of cells rather than hard-
ware thus represents the direction that 
genetics research will likely continue 
in the near future. Not only does this 
avoid ethical controversies, but also 
the techniques and knowledge to do so 
are already well understood. Given this 
understanding and the large amount 
of government funding and com-
mercial interest, the field of synthetic 
genetics will only continue to grow.
References
1. Synthetic Genome Brings New Life to 
Bacterium (20 May 2010). Available at http://
www.sciencemag.org/content/328/5981/958.full 
(24 March 2011).
2. Synthetic Bacterial Genome Takes Over 
Cell (20 May 2010). Available at www.nytimes.
com/2010/05/21/science/21cell.html (23 March 
2011).
3. D. Gibson et al., Science. 328, 52-56. (2010).
4. JCVI: First Self-Replicating, Synthetic 
Bacterial Cell Constructed(20 May 2010).
Available at http://www.jcvi.org/cms/press/
press-releases/full-text/article/first-self-
replicating-synthetic-bacterial-cell-constructed-
by-j-craig-venter-institute-researcher (23 March 
2011).
5. Scientists Create First Synthetic Cell (21 
May 2010). Available at http://online.wsj.com/
article/SB100014240527487035590045752564
70152341984.html (28 March 2011).
6. JCVI: Research / Projects / First Self-
Replicating Synthetic Bacterial Cell / Frequently 
Asked Questions (25 May 2010). Available at 
http://www.jcvi.org/cms/research/projects/first-
self-replicating-synthetic-bacterial-cell/faq/#q5 
(22 March 2011).
	11S_final.pdf