Communications of the ACM

in plants and introduce designer animals and humans. Says Daniel Gibson, vice president of DNA Technologies at Synthetic Genomics, Inc. and associate professor at the J. Craig Venter Institute, a leading genome research center: “As with any new area of science and technology, synthetic genomics has the potential for great societal benefit, but also the potential for harm.”

Beyond the Test Tube

Since the beginning of time, humans have focused on altering the genetic code of plants and animals through selective breeding, hybridization, and other techniques. Modern computing and science have taken the concept to an entirely new level, allowing researchers to achieve results that were previously impossible, or to compress years, decades, and even centuries of gene editing research into weeks or months by rearranging genes and redesigning biological pathways.

Modern synthetic biology is rooted in research from the turn of the current century. At that time, researchers Jim Collins and Tim Gardner of Boston University found a way to create a “toggle switch” with E. coli bacteria; essentially, the engineered cells could hold and maintain a single bit of memory. Around the same time, researchers Michael Elowitz and Stan Leibler of Princeton University built a ring-oscil-lator that allowed a cell to operate like a mini-clock. “This showed that it was possible to program complex, artificial functions into cells,” Lu points out.

Unlike silicon computing, which
relies on ones and zeros to build code
into software, biological systems re-
quire circuits engineered from DNA,
RNA, and proteins. “The DNA interacts
with proteins and RNA inside the cell,
and the collision between these differ-
ent parts is what leads to our ability to
compute information,” Lu explains.
“One challenge with biological sys-
tems is that, unlike silicon where you
can wire together components and en-
sure they are isolated from the rest of
the world, it’s not easy to do this with
biological systems. In addition, they
aren’t modular by default; it becomes
more of an analog programming task.”
To be sure, programming biology
is inherently challenging. “Building
circuits inside cells is not a highly scal-
able approach. The amount of energy
that a cell needs to drive different cir-
cuits is quite significant,” says Herbert
Sauro, an associate professor of bioen-
gineering at the University of Washing-
ton. “Unlike electrical systems, there’s
a scalability issue and the fact that you
need more and more independent pro-
teins to build larger and larger circuits.
Evolution did not build large comput-
ing systems inside a cell. It had to go
beyond the cell and create a multi-
cell system, such as the brain, to gain
enough computing power Ultimately,
every ‘transistor’ in biology has to be
unique, so this limits the size of things
you can do.”
Yet, knowledge of synthetic biology
is advancing at a rapid pace. Better heu-
ristic methods, new design tools, more
powerful computers, and increasing
big data capabilities are transform-
ing the field. One of the most impor-
tant breakthroughs came with a gene-
editing tool called CRISPR, which
“finds the right place in the genome—
out of 3 billion places—and cuts it,”
says George Church, a professor of
genetics at Harvard Medical School.
Essentially, the technology allows re-
searchers to expand their toolkit be-
yond merely adding genes; it lets them
delete or change genes to suit their
needs. Today, CRISPR is widely used
for research on humans, animals, and
plants. It is inexpensive, typically cost-
ing less than $100 in a lab that is al-
ready set up for standard molecular bi-
ology, and many government agencies
around the world have accepted the
technology. “They are saying it doesn’t
need to be regulated,” Church adds.

The combination of CRISPR tech-
nology, its low cost, and the ability to
avoid government regulation has im-
portant ramifications. For example,
in the agricultural space, CRISPR is
“a non-GMO way to do very precise
editing,” Church explains. This could
reduce the need for lengthy, and
sometimes expensive, testing. Geneti-
cally designed foods, such as corn,
soybeans, and potatoes, could be com-
mercially available within five years.
Many of these crops would be easier
to grow, more drought-resistant, and
more resistant to insects and diseases.
They might also grow faster and pro-
duce larger yields.

However, the concept goes far beyond field crops. A U.S. company, Recombinetics, is currently using CRISPR and a related technology dubbed TALEN to produce dairy cattle without horns, making them easier to handle. Meanwhile, synthetic biology is now being used to identify spoiled or infected food, and researchers in China have engineered beagles with about double the typical muscle mass, making them suitable for police and military work. Guangzhou General Pharmaceutical Research Institute boasts it produces between 2,000 and 2,500 of these dogs annually.

Yet, much of the work in synthetic biology centers on humans. For instance, Church is working on the complex task of programming pig genomes so pig organs such as livers, kidneys, hearts, and lungs would be compatible with humans, thus expanding the current boundaries of transplantation. He and others are also focusing on developing virus-resistant cells that could be used to eliminate mosquitos or their ability to carry Malaria, which currently kills upward of 650,000 humans per year. “It would target a very small fraction of about 3,500 species of mosquitos,” he explains.

In fact, the possibilities are limited only by the creativity and ingenuity of research teams and further advances in the science, Church says. “The technology could have a profound impact on health and medicine. It’s likely that we will begin to see clinical trials in programmable biology and, after testing gene therapies in animals, move forward to a small set of humans. If it is effective within that group, it will then move onto a larger set of humans.”