PLoS Medicine | www.plosmedicine.org183
incentives and commercial pharmaceutical houses have made
Western health care the envy of the world, the commercial
model only works if companies can sell enough patented
products to cover their research and development (R&D)
costs. The model fails in the developing world, where few
patients can afford to pay patented prices for drugs.
It is easy and correct to say that Western governments could
solve this problem by paying existing institutions to focus on
cures for tropical diseases. But sadly, there does not appear to
be enough political will for this to happen. In any case, grants
and patent incentives were never designed with tropical
diseases in mind.
Two main kinds of proposals have been suggested
for tackling the problem. The fi rst is to ask sponsors—
governments and charities—to subsidize developing-country
purchases at a guaranteed price [2,3,4]. The second involves
charities creating nonprofi t venture-capital fi rms (“Virtual
Pharmas”), which look for promising drug candidates
and then push drug development through contracts with
corporate partners. In this article, we discuss the limitations
of these two approaches and suggest a third, “open source,”
approach to drug development, called the Tropical Diseases
Initiative (TDI). We envisage TDI as a decentralized,
Web-based, community-wide effort where scientists from
laboratories, universities, institutes, and corporations could
work together for a common cause (see www.tropicaldisease.
nly about 1% of newly developed drugs are for
tropical diseases, such as African sleeping sickness,
dengue fever, and leishmaniasis . While patent
Why Open Source?
The idea behind asking sponsors to subsidize developing
country purchases at a guaranteed price is that this will prop
up drug prices and restore incentives for developing new
drugs [2,3,4]. In other words, it is a way of fi xing the patent
problem. However, subsidies have an important weakness:
it is almost impossible to determine correctly how large
the subsidy should be. In principle, the most cost-effective
solution is to set a subsidy that just covers expected R&D
costs. But how large is that? R&D costs are very poorly known,
with the published estimates quoting uncertainties exceeding
$100 to $500 million per drug. If the subsidy is set too low,
companies cannot cover their R&D costs and nothing will
happen. Set the subsidy too high, and the sponsor’s costs
skyrocket. To date, no sponsor has tried to implement these
In the “Virtual Pharma” approach, governments and
philanthropies fund organizations that identify and help
support the most promising private and academic research.
Examples include the Institute for One World Health (www.
iowh.org), a not-for-profi t pharmaceutical company funded
mainly through private sources and the Gates Foundation,
and the Drugs for Neglected Diseases Initiative (www.dndi.
org), a public sector not-for-profi t organization designed
to mobilize resources for R&D on new drugs for neglected
Virtual Pharmas have clearly started to bear fruit, and
are responsible for most candidate treatments for tropical
diseases currently under development. For example, the
Drugs for Neglected Diseases Initiative has a portfolio of nine
projects spread out across the drug development pipeline
for the treatment of leishmaniasis, sleeping sickness, Chagas
disease, and malaria . But Virtual Pharmas face three
important problems. The fi rst is similar to the problem
faced by subsidy proposals: guessing private-sector R&D
costs. One needs to understand what a product costs in
December 2004 | Volume 1 | Issue 3 | e56
The Neglected Diseases section focuses attention either on a specifi c disease or
describes a novel strategy for approaching neglected health issues in general.
Open access, freely available online
Citation: Maurer SM, Rai A, Sali A (2004) Finding cures for tropical diseases: Is open
source an answer? PLoS Med 1(3): e56.
Copyright: © 2004 Maurer et al. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original work is
Abbreviations: R&D, research and development; TDI, Tropical Diseases Initiative
Stephen M. Maurer is in the Goldman School of Public Policy, University of California,
Berkeley, California, United States of America. Arti Rai is in the School of Law, Duke
University, Durham, North Carolina, United States of America. Andrej Sali is in the
Departments of Biopharmaceutical Sciences and Pharmaceutical Chemistry and
the California Institute for Quantitative Biomedical Research, University of California,
San Francisco, California, United States of America.
Competing Interests: The authors declare that they have no competing interests.
*To whom correspondence should be addressed. E-mail: firstname.lastname@example.org
Finding Cures for Tropical Diseases:
Is Open Source an Answer?
Stephen M. Maurer*, Arti Rai, Andrej Sali
Box 1. Possible Licenses for TDI Discoveries
▪ A public-domain license that permits anyone to use the
information for any purpose.
▪ Licenses similar to the Creative Commons Attribution License
(http://creativecommons.org/licenses/by/2.0) that permit
anyone to use the information for any purpose, provided proper
attribution is given.
▪ Licenses such as the General Public License (www.opensource.
org/licenses/gpl-license.php) that prohibit users from seeking
intellectual property rights.
▪ Licenses that permit commercial companies to obtain and
exploit patents outside the developing world. These would allow
Virtual Pharma to stretch its own R&D funds by letting corporate
partners sell patented products to ecotourists, governments, and
other consumers living in the industrialized world.
PLoS Medicine | www.plosmedicine.org 184
order to negotiate the best possible price—and guessing
wrong is likely to be expensive. Second, Virtual Pharma’s
development pipelines will run dry with out more upstream
research. Research has been particularly weak in exploiting
genomic insights . Third, tropical disease research is badly
underfunded. For this reason, Virtual Pharma cannot succeed
without rigid cost containment.
We believe that a new, com munity-wide consortium, the
Tropical Disease Initiative, can help solve these problems. Its
success would help keep Virtual Pharma’s R&D pipeline full.
Furthermore, it would use open-source licenses to keep its
discoveries freely available to researchers and—eventually—
manufacturers. As we explain below, well-designed open-source
licenses are the key to containing Virtual Pharmas’ R&D costs.
While we expect the fi nal choice of license to be made
by TDI’s members, the guiding principle should be to pick
whatever license lets developing country patients derive the
most benefi t from TDI’s work. Possible choices are shown in
How It Works
To date, open-source methods have made little headway
beyond software . However, computing and computational
biology are converging. In the same way that programmers
fi nd bugs and write patches, biologists look for proteins
(“targets”) and select chemicals (“drug candidates”) that bind
to them and affect their behavior in desirable ways. In both
cases, research consists of fi nding and fi xing tiny problems
hidden in an ocean of code.
What would open-source drug discovery look like? As with
current software collaborations, we propose a Web site where
volunteers use a variety of computer programs, databases,
and computing hardware (Figure 1). Individual pages would
host tasks like searching for new protein targets, fi nding
chemicals to attack known targets, and posting data from
related chemistry and biology experiments. Volunteers could
use chat rooms and bulletin boards to announce discoveries
and debate future research directions. Over time, the most
dedicated and profi cient volunteers would become leaders.
Ten years ago, TDI would not have been feasible. The
difference today is the vastly greater size and variety of
chemical, biological, and medical databases; new software;
and more powerful computers. Researchers can now identify
promising protein targets and small sets of chemicals,
including good lead compounds, using computation
alone. For example, a SARS protein similar to mRNA cap-
1 methyltransferases—a class of proteins with available
inhibitors—was recently identifi ed by scanning proteins
encoded by the SARS genome against proteins of known
structure . This discovery provides an important new
target for future experimental validation and iterative lead
optimization. More generally, existing projects such as the
University of California at San Francisco’s Tropical Disease
Research Unit (San Francisco, California, United States)
show that even relatively modest computing, chemistry, and
biology resources can deliver compounds suitable for clinical
trials . Increases in computing power and improved
computational tools will make these methods even more
powerful in the future.
Just as they do today, Virtual Pharmas would choose
the best candidates. The difference is that open-source
drugs could not be patented in developing countries. This
would not stop Virtual Pharma from developing promising
discoveries. (S. Nwaka, V. Hale, personal communications).
Importantly, TDI would be a great boost to the efforts of
Virtual Pharmas, because it would help to contain the costs of
discovering, developing, and manufacturing drugs.
TDI would contain costs in three important ways. First, TDI
would ask volunteers to donate their time (and any patentable
discoveries) to the collaboration. Instead of fi nancial
incentives, TDI would offer volunteers non-monetary rewards,
such as ideological satisfaction, the acquisition of new skills,
enhancement of professional reputation, and the ability
to advertise one’s skills to potential employers. Software
collaborations have demonstrated that these incentives are a
good way to attract and motivate programmers . Similar
incentives should work equally well for biologists, chemists,
and other scientists.
Second, we have already pointed out that existing proposals
have diffi culty containing costs. The root cause is patents.
Normally, society relies on competition to keep prices low.
Patents—by design—short-circuit competition by giving the
owners the legal right to prevent others from using (or even
developing) their invention. TDI, on the other hand, would
restore competition by making drug candidates available to
anyone who wanted to develop them. We expect sponsors to
exploit this advantage by signing development contracts with
whichever company offers the lowest bid. Such competitive
bidding is a powerful way to contain costs, and is also a
good way to develop drugs. Virtual Pharma has extensive
experience supervising contract research.
Third, the absence of patents would continue to keep
prices low once drugs reached the market. The generic drug
industry shows what happens once drug makers are allowed
to compete. US drugs frequently fall to about one-third their
original price when patents expire .
Intellectual Property Rights
Would universities and corporations really let their people
volunteer? Won’t they insist on intellectual property rights?
The practical answer is that sensible managers do not care
December 2004 | Volume 1 | Issue 3 | e56
Figure 1. The TDI Model of Online Collaboration
PLoS Medicine | www.plosmedicine.org 185
about intellectual property rights unless they expect to earn
a profi t. This explains why sophisticated university licensing
offi ces seldom bother to interfere with open-source software
projects that are not commercially valuable . The same
logic would apply to open-source drug discovery. We would
hope that life sciences companies would make a similar
calculation. But permitting employees to participate is only
the beginning. We think that universities and companies
will also donate the data, research tools, and other resources
needed to make TDI even stronger. The reason, once again,
is that they have little to lose. The value of their intellectual
property depends almost entirely on US and European
diseases. For this reason, it costs very little to share their
information with tropical disease researchers. In fact, drug
companies already do this . TDI’s main challenge will
be to show donors that an open-source project can keep
members from diverting donated information back into the
commercially lucrative diseases that affect patients in the
Finally, there are precedents for private companies
developing drugs off patent. During the 1950s, March
of Dimes (see www.marchofdimes.com) developed polio
vaccines without any patents at all . It then signed
guaranteed purchase contracts with any drug maker willing to
develop commercial-scale production methods. The incentive
may not have been conventional, but it worked. And why not?
The contracts made good business sense: contract profi ts may
have been small compared to the profi ts on patented drugs,
but so was the risk. Fifty years later, contract research still
makes sense. Generic drug companies, developing world drug
manufacturers, contract research organizations, and biotech
fi rms have all said that they would consider contracts to
develop open-source drug candidates. (M. Spino, S. Sharma,
F. Hijek, and D. Francis, personal communications).
So far, we have described a shoestring operation that exists
mainly on the Web. Except for computer time, budgets would
be more or less the same as existing software collaborations.
Computing would be expensive but manageable. Today’s
biologists routinely scrounge resources from university
machines or borrow time on home computers [16, 17].
This Web-centric approach would be a good start, but not a
complete solution. Computational biology works best when
it can interact with experimental chemistry and biology.
Nevertheless, a low-budget computational approach is
probably enough to generate new science, suggest ideas
for follow-up experiments, and make new drug candidates
available under licenses designed to yield maximum benefi t
to the developing world.
In practice, an open-source drug discovery effort is likely
to include modest experiments. Many academic scientists
control discretionary resources and, in some cases, tropical
disease grants. Furthermore, good science generates its
own funding. We expect experimentalists to turn the
collaboration’s Web pages into grant proposals.
That said, TDI’s volunteers will be most productive if
sponsors back them. Charities could support open-source
drug discovery by making wet chemistry and biology
experiments a top priority. Corporations could also help by
donating funds, laboratory time, or previously unpublished
results. One low cost/high value option would be for
companies that have already tried a particular research
direction to warn TDI if the collaboration was about
to investigate a known dead end. (R. Altman, personal
Open-source drug discovery is feasible—that is, no known
scientifi c or economic barrier bars the way. But what are the
risks? Experience with software collaborations highlights
the main social and economic challenges. First, the project
will have to fi nd and motivate volunteers. Based on existing
software collaborations, we estimate a required minimum
“critical mass” of a few dozen active members. Second,
modest chemistry and biology experiments will be needed
to increase the chances for success. Resources of several
hundred thousand dollars per year—mostly in the form
of in-kind donations of databases, laboratory access, and
computing time—would make open-source drug discovery
much more powerful. By most standards, such risks are real
The largest uncertainties are scientifi c. Can a volunteer
effort based on computational biology and modest
experiments produce the high-quality drug candidates
that Virtual Pharma needs? A successful program must
(1) make a signifi cant contribution toward supplying the
genomic insights that tropical disease research needs to move
forward, and (2) make useful drug candidates available for
development and production under open-source licenses.
Open-source drug discovery looks feasible. The only way to be
sure is to do the experiment—and we invite you to join us. ?
To learn more about TDI or to volunteer, go to http:⁄⁄www.
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