8/17/2019 The Lancet - Can Open-Source Drug Development Deliver?

1/2

World Report

www.thelancet.com 

Vol 387 May 14, 2016 1983

Can open-source drug development deliver?

Open-source drug development involves open data sharing, collaboration, and results sharing.

The aim is to produce new drugs for neglected diseases. But can it work? Tatum Anderson reports.

A research chemist has a problem.He wants to make a better versionof an existing drug that comes as amixture—one with side-effects anda horrible taste. But it is a drug fora neglected disease, so it’s unlikelythat a pharmaceutical company willstep in to work on it. So, he posts

the problem on the internet, andsolutions begin to appear fromscientists around the world. Usingthem, he modifies the molecule inhis laboratory and posts results backonline for them to critique. Gradually,a pure tasteless form without side-effects is developed and handed to amanufacturer for production.

This is how open-source drugdevelopment is supposed to work.It is a concept borrowed from the ITworld, which harnessed a voluntary

global army of coders to producesoftware for a fraction of thedevelopment costs of commercialrivals. Open-source methods speedup drug discovery and could makedrugs far more affordable, saysMatthew Todd, the scientist at theUniversity of Sydney, Australia, whohas posted just such a drug—againstschistosomiasis—on the internet andis now working on two open-sourcemalaria molecules.

Specifically, open-source methods

widen the pool of researchers applyingtheir expertise to a problem and cutdown duplication. And just like open-source software, any modificationsare also open and not patented. “Thequestion is whether it was worthabandoning secrecy to get input frompeople. And, yes, it is worth it becauseresearch is accelerated by strangers”,Todd tells The Lancet.

Alternative wayTodd is taking the concept further; he

has helped establish the Open Source

Pharma Foundation (OSPF), whichwill develop open-source drugs andrun the first open-source clinical trials.It plans to establish an alternativedrug discovery route for neglecteddiseases where the research anddevelopment (R&D) incentive is weak.“We are unrealistic in expecting tools

for something [like] Ebola to arisefrom the private sector. It’s just not inthe business plan”, he says. “We needother ways to generate the [drugs]that are going to help us.”

OSPF is a fledgling organisationwith credentials. Founders includeBernard Munos, ex-adviser on

corporate strategy at Eli Lilly, and Jaykumar Menon of McGil l University,Canada, a human-rights lawyer whohas turned his attention to drugs forneglected diseases. Ex-head of R&D atAstraZeneca India, Tanjore Balganesh,will run product developmentpartnership (PDP) for OSPF to managedevelopment and manufacturingfrom Bangalore, India.

The wider global health com-munity—from Médecins SansFrontières to Sanofi-Aventis—has

attended its meetings, a roadmapis agreed, and seed funding securedfrom India’s Tata Trusts. “We are goingto prove that there is an alternate wayby applying open-source principlesat each stage of the process”, saysMenon. So, for clinical trials, OSPFwill use existing platforms; includingone that crowdsources clinical trialprotocols and an online laboratorynotebook that allows data to beregularly posted from clinical trials.OSPF will also work with the European

and Developing Country Clinical

Trials Partnership, which runs clinicaltrials for neglected diseases in Africa.Menon says their clinical trial costswill be significantly less than pharma’sby using open platforms, carryingthem out in cheaper, endemiccountries, and securing innovativefunding schemes.

Old rootsOSPF is not the only drug projectusing open methods. It is actually adirect descendant of Open SourceDrug Discovery (OSDD), an IndianGovernment consortium thathas, since 2008, led thousands ofacademics and undergraduatesacross India to work on tuberculosis(Balganesh was OSDD’s project head).

Open source has been tried for overa decade, spawning Cambia’s open-

patent database and Medicines forMalaria Venture (MMV)’s PathogenBox project among others; MMV postspathogen boxes—400 compoundsthat could combat pathogenscausing some of the world’s mostneglected diseases—to researchgroups worldwide in return for acommitment to put results in thepublic domain within 2 years (aprecursor—the Malaria Box—hasalready led to 30 published papers).

“Open-source methods speed up

drug discovery and could make

drugs far more affordable...”

    A   s   s   o   c    i   a    t   e    d    P   r   e   s   s

8/17/2019 The Lancet - Can Open-Source Drug Development Deliver?

2/2

1984 www.thelancet.com 

Vol 387 May 14, 2016

World Report

Open source is popular too; civil

society organisations in Marchproposed support for it within the

 Johannesburg Declaration present edto the UN Secretary-General’s high-level panel on access to medicines.WHO’s Consultative Expert WorkingGroup recommended more open-source approaches to R&D andinnovation too; MMV’s project is aWHO demonstration project designedto test such approaches.

Proponents say that open-sourcemethods are needed because

research fiefdoms have built uparound neglected diseases andstalled progress towards new drugs.Researchers have refused to sharedata during some outbreaks fearing,among other reasons, that they’d

 jeo par dis e the ir own chances forpublication; universities rush topatent discoveries even for neglecteddiseases.

Individual researchers are trying openconcepts; some are publishing straightto the internet. Research chemist

Isaac Yonemoto,  has crowdfundedProject Marilyn—research on anabandoned molecule, which mighthave oncological effects. He regularlyposts results online so that they cannotbe patented and began testing in amouse model this month.

So-called biohackers are workingon devising a simpler and cheapermethod to create insulin for thosewho cannot afford it, includingpoorer Americans. Many work intheir spare time at Open Insulin’s

California laboratories, which havebeen crowdfunded. Pharmaceuticalcompanies are even opening theirdrug libraries to outside scientists.

Despite the number of openp r o je ct s , m o s t co n ce n t r at eon the preclinical stages ofdrug development. None haveproduced drugs. ”Nobody is doingdrug discovery for neglecteddiseases in the open”, saysAled Edwards, CEO of StructuralGenomics Consortium, which

resolves the structure of potential

drug targets, develops inhibitors

(possible protodrugs), and poststhem to researchers and into thepublic domain. He plans an alternativeopen-source business model thatgoes beyond the preclinical stageand passes molecules to commercialmanufacturers after the proof-of-concept stage, so that they canundertake and pay for phase 3 trials.

Previous projects probablyunderestimated how ferociouslycomplex drug discovery is comparedwith software. Development is moreexpensive too, especially, for clinicaltrials. So once an open moleculelooks promising, it or variations ofit often disappear into commercialdevelopment, are patented, and takenout of the public domain.

Truly open source?Open-source labels are oftenmisleading anyway; opennessmight only apply to a tiny portionof the development cycle, saysChristine Årdal of the NorwegianInstitute of Public Health, who hasstudied several so-called open-sourceprojects. “It might be very trendy tosay that it’s open source when in factit’s not”, she says. If a project can boastopen data sharing, collaboration,and rules that ensure results remain

open too, it’s probably open source.If problems are placed in the publicdomain but the solutions are not,that’s open innovation, she says.

Årdal argues that even OSDD—hailed as one of the greatest open-source projects so far—is actuallycrowdsourcing because it ownseverything that is discovered, and theresults are not always easily accessibleto the wider community to critique orwork on.

Labelling a project open source

brings great PR and kudos. But it’s

undeserved if the project merely

rehashes age-old scientific methodssuch as collaborations between grant-funded scientists who would alreadybe working in the field anyway. Sosays Stephen Maurer, of the Universityof California, Berkeley, USA, who firstproposed the open-source TropicalDisease Initiative as far back as 2004.

True open source should insteadunleash talents not already there;the enthusiasm of scientists withday jobs who love problem solvingor doing altruistic work in their spare

time; female scientists excluded fromthe workplace who can manipulatemolecules on home computers, oreven companies that undertakepro-bono work on open-sourceprojects to impress potential clients,he says. Importantly, it must be aviable alternative to pharmaceuticalcompanies. ”The definition shouldmean something. We are trying todesign a new institution that performsbetter than what we already have”,he says.

So now OSPF must prove it canbring a drug to market. Fine details willbe worked out; pricing models shouldensure individual researchers’ effortsare vetted and properly attributed.And, importantly, the public fundsthat it believes are available for opensource need to materialise.

That’s why OSPF’s first clinical trialswill focus on repurposed drugs; someexisting drugs developed for onedisease often show promise againstothers (an epileptic drug might work

against tuberculosis, for instance).Bruce Bloom, president and chiefscientific officer of US repurposingorganisation, Cures Within Reach,which is working with OSPF, saysrunning trials of repurposed drugscan c ost as little as US$500 000and take just 3–5 years to complete.Funders and the larger global healthcommunity will be more inclined toback open source if they can see a realdrug, says Todd.

Tatum Anderson

“.... fiefdoms have built up

around neglected diseases and

stalled progress towards new

drugs.”