1. 342 www.thelancet.com/oncology Vol 13 April 2012
Cancer and Society
For more on Foldit see http://
fold.it/portal/
For more on the design of
cancer drugs see http://fah-
web.stanford.edu/cgi-bin/
fahproject.overusingIPswillbeba
nned?p=10113
For more on the human
telomerase RNA pseudoknot
see http://pubs.acs.org/doi/
full/10.1021/ja2092823
For more on SETI@Home see
http://setiathome.berkeley.edu/
Scientific discovery has never been
a solitary endeavour. Through the
collaboration of great minds, man has
set foot on the moon, split the atom,
and discovered the building blocks of
life. Such advances have opened the
floodgates of technology and enabled
society to thrive. But in keeping with
Newtonian logic, these beneficial
advances also have equally negative
consequences: including global warm-
ing, unsustainable population growth,
andlossofbiodiversity.Canwecontinue
to relyon a small groupof scientists and
thought leaders to solve the world’s
problems? Probably not (and with a
population of 7 billion, why should
we?). If everybody could contribute
their knowledge, expertise, and time,
then perhaps these problems could be
solved much faster.
This idea of open collaboration has
recentlybeenharnessedinavideogame
called Foldit to create the first
crowdsourced redesignof a protein:the
Diels-Alderase enzyme. Players were
introduced to a series of puzzles in the
formof complex protein structuresthat
they could tinker with. The aim was to
create a stable chain of aminoacids; the
more stable the chain, the more points
awarded.What resulted was an enzyme
with more than 18-fold higher activity
than the original. Previous attempts
to design a more efficient version
of the Diels-Alderase enzyme were
unsuccessful. So, researchers turned to
the public for help. Although personal
computers can do billions of complex
calculations per second, they are unable
to accurately identify complex shapes.
Instead, our spatial awareness and
creativity perfectly equips us with the
abilityto solve such conundrums.
Crowdsourced gaming of this kind
could be used to tackle molecular-
scale design problems; for example,
in the design of cancer drugs and
for improving our understanding of
P53, a protein that is altered in many
cancers, and protein chaperones, that
contribute to protein folding, which
when deregulated are also associated
with cancer.
However, Samuel Cho, a biophysicist
and computer scientist at Wake Forest
University (Winston-Salem, NC, USA),
has also shown the technology used
to develop videogames can be put to
good use in cancer research without
relying on humans to do the hard parts.
Using videogame graphics processing
units, Cho simulated the folding of
human telomerase RNA pseudoknot.
“A normal cell shortens its DNA after
every replication so that a cell knows
when to die. The telomerase enzyme,
however, keeps adding bits of DNA
so that the cell doesn’t know when to
stop replicating, resulting in tumours
that lead to cancer”, explains Cho. “Our
simulations provide a new molecular-
resolution picture of the folding
mechanism of the telomerase enzyme
RNA pseudoknot, which is well known
to be critical for telomerase enzyme
activity.”With such improvement inthe
understanding of telomerase structure
and function, new targets for cancer
drugs could be explored.
Cho even suggests that the power of
his simulations could be increased by
using crowdsourcing methods similar
to those used by the SETI@Home
project, which employs the processing
power of thousands of personal
computers to analyse data gathered
from radiotelescopes in search for
extraterrestrial life.
One of the most successful applica-
tions of open innovation and crowd-
sourcing for scientific discovery arose
from the most unlikely of places,
thepharmaceuticalindustry—infamous
for its fierce defence of intellectual
property rights. In 2001, Eli Lily funded
a project called InnoCentive, which is a
platform allowingorganisationsto post
scientific challenges to a community
of millions of problem solvers (mainly
scientists and engineers). In exchange
for solutions, these organisations offer
prize money.
Pharmaceutical companies have
realised that no matter how much
money they put into research and
development of blockbuster drugs,
innovation and productivity does not
necessarily increase. “The blockbuster-
drug business model certainly has
not lacked either high incentives on
part of the drug companies or high
investment”, observes Karim Lakhani,
a specialist in the management of
technological innovation at Harvard
Business School (Boston, MA, USA).
“The issue we are facing is really more
ofknowledgeaccessandfindingunique
solutionstotough problems.”
Targeting cancer is on InnoCentive’s
radar. Some of the most recent
challenges posed include the develop-
ment of chondroma cell lines, faster
DNA and RNA sequencing of a single
cancer cell, and modelling of the
functional molecular networks in
cancer cells. However, the approach
used by InnoCentive is not entirely
altruistic. In exchange for prize money,
problem solvers release the intellectual
property rights to InnoCentive and the
organisationthat posedthe problem.
“The baseline of the InnoCentive
model is that the prize should be
incentive enough for someone to
release their intellectual property”,
explains Lakhani. “Sharing intellectual
property is tough because it’s not clear
if the individual scientists or teams
have the resources or capabilities to be
able to take to market their intellectual
property and actually make money.”
By enabling individuals from around
the world to share their expertise,
crowdsourcing is broadening the
horizons of cancer research. Perhaps
the next big cancer discovery will come
fromyou.
Mario Christodoulou
Technology
Crowding out cancer
DavidMack/SciencePhotoLibrary