been tested on humans. The potential
side-effects and complications remain
unclear. Unlike insects, human beings
and other mammals will be more difficult to penetrate due to their higher
levels of infection-fighting nucleases,
but researchers are continuing to work
on solutions to that problem.
That work will require increasingly
complex computer modeling, almost
certainly involving more custom application development. Indeed, most
of the high-profile synthetic biology
work—and funding—has focused on
the “application” layer of high-profile
solutions, rather than on the far-less-glamorous systems layer that would
ultimately enable more and more of
these applications to take shape.
“Historically, the engineering toolkit for biotechnology has not been
well-defined,” says Endy, who laments
the lack of funding support—and apparent interest—in tackling these in-frastructure-layer challenges in both
the academic or corporate worlds.
None of the major university computer science departments devote significant support to synthetic biology,
nor (apart from Autodesk) does there
seem to be much interest emanating
from the corporate software world.
“Teams that get funded to work on
solving problems with biology tend to be
overdriven by the immediate pressing
nature of the situation,” says Endy. “That
leads to a bias in funding and under-
development. We are too focused on
Endy feels the answer may lie in
public-private partnerships, similar to
the ones he forged with BIOFAB, which
pioneered the development of an open
source framework known as BIOBRIC,
something akin to a Creative Com-
mons license for biological parts.
“Public-private partnerships can
work in biotechnology by allowing aca-
demics and professionals to work to-
gether in an effective way.” says Endy.
“Academics are in the business of ship-
ping papers, and biotech companies
are over-driven by implementation.”
Endy sees potentially enormous com-
plementary power at work when the
corporate work ethic gets coupled with
the academic commitment to getting
the fundamentals right.
Moreover, biologists and computer
scientists still need to learn how to
speak each other’s languages. DNA
may be a programming language, but
it does not involve a binary system;
instead, it is an ordinal system, involving a more complex code of nucleotide sequences. And while most
computer programming languages
are linear, time-based systems, biology happens in the physical world; it’s
a four-dimensional proposition.
Taking computer science from the
binary realm of silicon into the four-dimensional, ordinal biological world
will inevitably require a steep learning
curve, but the potential payoff for humanity is enormous. Says Endy: “The
number of miracle moonshots is almost infinite.”
Amir, Y., Ben-Ishay, E., Levner, D.,
Ittah, S., Abu-Horowitz, A., Bachelet, I.
Universal Computing by DNA origami robots
in a living animal. Nature Nanotechnology. 9,
353-357 (2014). doi: 10.1038/nnano.2014.58.
Douglas, S.M., Bachelet, I., Church, G.M.
A Logic-Gated Nanorobot for Targeted
Transport of Molecular Payloads. Science.
Mutalik, V., Guimaraes, J., Cambray, G.,
Lam, C., Christoffersen, M.J, Mai, Q., Tran, A.B.,
Paull, M., Keaslking, J.D., Arkin, A.P., Endy, D.
Precise and reliable gene expression via
standard transcription and translation
initiation elements. Nature Methods. 10:
354-360 (2013). doi: 10.1038/nmeth.2404
Sissel, J., Iacovelli, F., Falconi, M., Kragh,
S., Christensen, B., Frøhlich, R., Franch, O.,
Kristoffersen, E., Stougaard, M., Leong, K. W.,
Ho, Y., Sørensen, E.S., Birkedal, V., Desideri, A.,
Temperature-Controlled Encapsulation and
Release of an Active Enzyme in the Cavity
of a Self-Assembled DNA Nanocage, ACS
Nano, 2013, DOI: 10.1021/nn4030543
Alex Wright is a writer and information architect based in
© 2015 ACM 0001-0782/15/04 $15.00
known as Cadnano to accelerate the
The work paid off, and soon researchers in his lab were able to complete dozens of designs per month,
when previously they were only completing one. They soon began to take
on more challenging design projects.
One project originated with Douglas’ work on DNA as a graduate student
at Harvard University in the mid-2000s,
working with collaborators Hendrik Di-etz and William Shish to create complex
shapes made out of DNA strands. By
manipulating the order of nucleotides
within the famous double-helix structure of DNA, they were able to influence
the way one strand interacted with another: in effect, programming them to
bend, join together, and combine into
Douglas continued to pursue his studies at Harvard with computational biology pioneer George M. Church and Ido
Bachelet, a researcher in experimental
pharmaceutics who would go on to lead
the work on DNA-based origami robots
at Bar-Ilan University. Eventually, they
began to work on progressively more
ambitious DNA experiments.
In 2012, Douglas and Bachelet
published a seminal article in Science
about their work, chronicling the results of their experiments in designing
an autonomous DNA nanorobot capable of delivering molecular “payloads”
to attack six distinct types of cancer
cells. Their study found this approach
worked particularly well with certain
kinds of leukemia cells, while leaving
99% of healthy cells untouched.
If successful, nanorobot-based cancer treatment would represent a huge
leap forward from the brute force therapies of traditional chemotherapy and radiation techniques, and promises to relieve the suffering and prolong the lives
of countless millions of cancer patients.
Elsewhere, researchers at Duke University, the University of Rome, and
Aarhus University have built a “DNA
nanocage” with tiny lattices that can
open and close in response to temperature signals. This mechanism would allow it to release enzymes in response to
environmental conditions, making it
theoretically possible to deliver highly
targeted medicines in pill form.
For all of their potentially enormous
promise, none of these devices has
“Cells are living,
“They are fully