The core feature of trusts-holding property for the benefit of others-is well suited to constructing a research community that treats reagents as public goods

Andrusiak, Kerry

Charney, Rachel

Chawaf, Arij Al

Cynader, Zarya

Edwards, Aled

ElDessouki, Ahmed

Lee, Yunjeong

Moeser, Andrew

Morgan, Max

Stern, Simon

Zuercher, William J.

English

Al Chawaf, Arij

Zuercher, William J

TSpace Repository

A trust approach for sharing research reagents

Carolina Digital Repository

SC I ENCE TRANS LAT IONAL MED I C I N E | FOCUSPOL I CY 2017 © The Authors,1Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada. 2Faculty of Law,University of Toronto, Toronto, Ontario M5S 2C5, Canada. 3Grand Challenges Canada, Toronto, Ontario M5G1L7, Canada. 4Gilbert’s LLP, Toronto-Dominion Centre, Toronto, Ontario M5K 1K2, Canada. 5Structural GenomicsConsortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC27599, USA.*Corresponding author. Email: aled.edwards@utoronto.caEdwards et al., Sci. Transl. Med. 9, eaai9055 (2017) 31 May 2017some rights reserved;exclusive licenseeAmerican Associationfor the Advancementof Science.DA trust approach for sharing research reagentsAled Edwards,1* Max Morgan,2,3 Arij Al Chawaf,1 Kerry Andrusiak,2 Rachel Charney,2Zarya Cynader,2,4 Ahmed ElDessouki,2 Yunjeong Lee,2 Andrew Moeser,2,4Simon Stern,2 William J. Zuercher5The core feature of trusts—holding property for the benefit of others—is well suited to constructing a researchcommunity that treats reagents as public goods.own at UNIVERSITY OF N. CAROLINA - CHAPEL HILL on August 16, 2019http://stm.sciencemag.org/loaded from In 1980, with the passage of the U.S. Bayh-Dole Act, the culture of academic sciencechanged. The act gave universities the re-sponsibility to manage their intellectualproperty for the betterment of society, withthe broad aim of translating more universitydiscoveries into products. In response, academicinstitutions created technology transfer officesto better manage their potential intellectualproperty and facilitate technology commerciali-zation (1). Predictably, as part of this moresophisticated approach to technology transferand partly in response to metrics of successthat included numbers of patents, institutionsgreatly expanded the range of discoveries thatthey deemed to have potential commercialinterest (2). Discoveries were patented at ratesnot seen previously, and assets such as bio-medical research reagents were shared only un-der legal material transfer agreements (MTAs)that placed restrictions on their commercialand, often, scientific use (3).MTAs have three main functions. The firstis to establish clear “chains of custody,” thusassuring the recipient that the material is notencumbered by background agreements orclaims. The second is to provide legal protec-tion for the provider. An MTA might include,for example, a clause that states that there isno guarantee that the material is actually safeor fit for particular purposes. The third func-tion is to establish conditions for use of thematerial. For example, the provider might insertconditions that restrict use or demand claimson future intellectual property.In aggregate, negotiations over such con-ditions cause substantial delays in the dis-tribution of research reagents. A universitymight execute thousands of MTAs each year,with an average delay to execution of a fewweeks and with exceptional delays of monthsand years. As a result, what was born as a so-lution for the perceived translational gap be-tween academia and industry has evolvedinto a widely applied and complex systemof legal agreements that often encumber eventhe most basic and commercially irrelevantbiomedical research (4). There are now stan-dard template agreements that have stream-lined the MTA process, but only a smallfraction of reagent exchange is done underthese standard MTAs. Examples of suchMTAs include the Uniform Biological MaterialTransfer Agreement (www.autm.net/resources-surveys/material-transfer-agreements/uniform-biological-material-transfer-agreement) andthe U.K. Brunswick MTA (www.arma.ac.uk/resources-1/research-contracts/material-transfer-human-tissue-agreements).In another attempt to accelerate science,some projects were established to generate re-search materials and make them available.Most focus on those materials that have lowcommercial potential and little chance of gen-erating new intellectual property. For exam-ple, the Mammalian Gene Collection projectcreated a repository of sequenced human com-plementary DNA clones that were made avail-able for a cost but without legal encumbrances(5). Other reagent-generating projects, such asthe Structural Genomics Consortium (6) (www.thesgc.org/chemical-probes), provide openaccess to reagents that have considerable com-mercial value and that also might be used togenerate patentable discoveries. The positionof the Structural Genomics Consortium is thatthese reagents would make a greater impact ifkept in the public domain, and the patenting ofdiscoveries using these reagents would restrictboth subsequent scientific discovery and com-mercial exploitation.We sought to develop a general mecha-nism to allow for the widest and least encum-bered use of research reagents. The existingstandard MTAs restrict the recipient fromtransferring the material to other scientists,and they also place restrictions on the useof the material commercially. To overcomethese limitations, we describe the concept ofan “open science trust” as a framework to shareresearch tools. The core feature of trusts—theholding of property for the benefit of others—is better suited than are bilateral contractualarrangements to the construction of a researchcommunity dedicated to treating experimentalreagents as public goods.THE TRUST DEVICEUnder an open science trust, reagents are treatedas a public-good resource governed by prin-ciples that promote the public interest, in thiscase, open science. Our open science trustagreement codifies these public-good princi-ples. Under its terms, a recipient of researchreagents becomes a “trustee” of the reagents.Trustees are bound by principles that specificallyprohibit filing any patent claims that would re-strict use of the reagents by others. The result isto create and expand an open science commu-nity connected by a common commitment tothe foundational aims of the reagent generators.A trust is a legal relationship whereby oneparty—called the trustee—is given controlover property but must use it for the benefitof others—called the beneficiaries. In this re-gard, a trust contrasts with direct legal owner-ship over property, which allows owners touse the property for their own ends and toprevent others from using or benefiting fromit. That is how we normally think about tan-gible goods such as real estate and intangibleones such as patented biomedical inventions.A trust places a duty on those who pos-sess entrusted assets to manage those assets1 of 3SC I ENCE TRANS LAT IONAL MED I C I N E | FOCUShttp://sDownloaded from for the benefit of particular third parties or, inthe case of charitable trusts, in furtherance ofparticular objects that benefit the public. Trustsare created by appointing trustees under a legaldocument that enumerates specific obligationsin dealing with trust property. Private trusts—those with individual beneficiaries—are oftenused for tax and estate planning purposes.Charitable trusts, by contrast, are dedicatedto serving the public, as opposed to partic-ular individuals, and must have definite char-itable objects that guide the trustee’s use oftrust property. In effect, the “public” consti-tutes the beneficiary of a charitable trust. Char-itable trusts are often administered by a groupof trustees whose joint efforts to further theaims of the trust can foster a communal senseof purpose. at UNIVERSITY OF N. CAROLINA - CHAPEL HILL on August 16, 2019tm.sciencemag.org/THE TRUST AS A TEMPLATE FOROPEN SCIENCEThe goal of our project is to provide the com-munity with tools and reagents without restric-tions on use. The open science trust concepthelps to achieve this end by appointing the re-cipient of research reagents as a trustee of thereagents, who commits to use them in a man-ner that serves the trust’s beneficiaries. Thesebeneficiaries include (i) the organization thatprovides the reagents, (ii) others in the scientif-ic community who may benefit from openaccess to the reagents and the results of the re-cipient’s research, and (iii) members of thegeneral public whose health might be aidedby subsequent discoveries.Whereas it is not, strictly speaking, a char-itable trust, the open science trust mechanismseeks to further open science principles for thepublic good in a similar spirit. Just as a trustdocument sets out particular conditions aimedat furthering the trust’s goals, the open sciencetrust lists a series of specific obligations that thetrustee accepts, including (i) the duty to placeresulting research and data in the public do-main and (ii) the duty not to seek or enforceintellectual property rights. Moreover, becausethe open science trust is not intended to inhibitdownstream innovation, it limits the enumer-ated obligations to the supplied material itself;the obligations do not extend to derivatives ofthe material that the trustee might create.These conditions were crafted to signal topotential recipients that they must embraceopen science principles. As a result, the openscience trust achieves two objectives. First, itallows a rapid means for researchers to accessand share enabling reagents. Second, it aggre-gates a community of researchers around theEdwards et al., Sci. Transl. Med. 9, eaai9055 (2017) 31reagents, expanding the scope of open scienceconducted with the reagents. The open sciencetrust differs in form and in spirit from the cus-tomary mechanisms to transfer materials be-tween institutions. When an MTA is used totransfer materials, the reagents are treated ascommercial goods. Such transactional interac-tions are often subject to lengthy negotiationand also convey to the recipient a sense of in-dividual ownership of the materials. By con-trast, the open science trust fosters a sense ofcommunity dedicated to serving the interestsof others.ENFORCING THE TRUSTCommonly, trusts are enforced through le-gal mechanisms: private trusts through thethreat of lawsuit by the beneficiaries andcharitable trusts through the actions of gov-ernment officials with jurisdiction over char-ities. In our concept of an open science trust,although its beneficiaries could, in theory,seek redress for violations of the trust con-ditions, we do not intend for this to occur.We anticipate that the sense of communityamong recipient trustees, and the norms thatare implicit, will become the mechanism toenforce the trust. We believe that the openscience trust’s provision for sharing resultswill evolve to become the expected practiceby the user community. In this context, pre-cisely because the open science trust modelseeks to encourage a sense of communal par-ticipation and to inculcate a set of sharedopen science norms among researchers, atrustee who does not abide by the terms ofthe trust would potentially face challengesto maintaining good standing within thecommunity. This, we imagine, will providestronger inducement to adhere to the prin-ciples than would the threat of legal action.The use of community norms to enforcebehavior has precedent. Norms, like law, serveto promote cooperation in a community byovercoming socially deleterious but individual-ly rational conduct. Scholars have shown thatsocial norms play an important role in in-ducing people to follow informal rules in a com-munity. As the property scholar R. Ellicksonshowed in a study of Shasta County ranchers,members of a community are more likely toobey their own informal laws than the officiallaws on the books, so long as the communitystands behind and enforces those informal laws.In Ellickson’s study, ranchers had their ownrules concerning responsibility for damage cre-ated by escaped cattle, and they used communalsanctions to enforce those rules (7). NormativeMay 2017systems of this nature have the advantage ofavoiding the high costs associated with legalenforcement.We see a strong analogy between Ellickson’sranchers and the biomedical research com-munity. Although research communities arenot geographically defined, as in Ellickson’sstudy, they display many of the same features:Members frequently interact both privatelyand publicly and share much the same senseof mutual dependence, making noncom-pliant members eligible for various informalsanctions—such as exclusion from conferencesand failure to be credited in research articles.These sanctions are likely to be more effectivethan a remote threat of legal enforcement, giv-en researchers’ and their institutions’ ongoingneed to maintain a profile in the community.Thus, although the trust document might seemto gesture toward a legal enforcement frame-work as its backdrop, its more salient effectcomes from the same set of communal valuesthat the open science trust concept itself seeksto promote.Laws and norms also influence one another,including in the area of biomedical research.For example, scientific research norms histor-ically promoted science in the public domain,but the Bayh-Dole Act and associated lawshave partially subverted these norms in favorof proprietary approaches (8). The open sciencetrust can be seen as an attempt to use law in-stead to revive, reinforce, and extend the preex-isting community norms around open science,specifically in the context of sharing reagents.A SAMPLE OPEN SCIENCETRUST AGREEMENTFor the past 5 years, the Structural GenomicsConsortium has used a “click-wrap” MTA(www.thesgc.org/chemical-probes/request)to distribute material with minimal obliga-tions. This MTA is principally designed toprotect this consortium against misuse ofthe reagents. Although this MTA requiresthe recipient to refrain from filing for intellec-tual property protection covering the reagents,and has been successfully used to distributethousands of reagents, it is structured as a bi-lateral contract and does not create an ex-panded community of researchers with ashared commitment to open science. The openscience trust agreement (OSTA) is the firstattempt by the Structural Genomics Con-sortium to deploy the open science trust mech-anism to disseminate research tools (www.thesgc.org/click-trust). In the OSTA, an intro-ductory section first describes the organization,2 of 3SC I ENCE TRANS LAT IONAL MED I C I N E | FOCUS at Uhttp://stm.sciencemag.org/Downloaded from creates the trust, and sets out its beneficiaries,which, in this instance, are the StructuralGenomics Consortium and its members, re-searchers in the scientific community, and in-dividuals in the general public who benefitfrom research with the entrusted material.A series of clauses then outlines the conditionsunder which the material is transferred. Themain differences between a standard MTAand the OSTA are that the OSTA (i) requiresthe recipient trustee to commit not to file forany intellectual property that covers aspectsof the material or its uses; (ii) requires the re-cipient to place the results from the use of thereagents into the public domain, through openaccess journals or on openly accessible web-sites, as rapidly as is possible; and (iii) grantsthe recipient the right to disseminate thematerial to additional recipients, provided thoserecipients agree to the terms of the OSTA.Most impediments to sharing research re-agents, even those of no commercial value, de-rive not from concerns about safety, researchprimacy, or the public good but rather fromconcerns about current and future ownershipof intellectual property. In early-stage drug dis-Edwards et al., Sci. Transl. Med. 9, eaai9055 (2017) 31covery research, the morass of agreements andcompeting intellectual property claims canhinder the progress of science and discovery.We anticipate that the open science trust mech-anism will reduce costly redundancies in early-stage research and allow universities andfunders to quantify the broader returns on theirresearch investments.REFERENCES AND NOTES1. D. A. Kirby, Creating entrepreneurial universities in theUK: Applying entrepreneurship theory to practice.J. Technol. Transf. 31, 599–603 (2006).2. Association of University Technology Managers (AUTM),AUTM Licensing Activity Survey Summary: FY2001Deerfield, IL (AUTM, 2001).3. V. Rodriguez, Material transfer agreements: Open sciencevs. proprietary claims. Nat. Biotechnol. 23, 489–491 (2005).4. T. Bubela, J. Guebert, A. Mishra, Use and misuse ofmaterial transfer agreements: Lessons in proportionalityfrom research, repositories, and litigation. PLOS Biol. 13,e1002060 (2015).5. R. L. Strausberg, E. A. Feingold, R. D. Klausner, F. S. Collins,The mammalian gene collection. Science 286, 455–457(1999).6. M. M. Jones, S. Castle-Clarke, D. Brooker, E. Nason,F. Huzair, J. Chataway, The Structural GenomicsConsortium: A knowledge platform for drug discoveryMay 2017(RAND Corporation, 2014); www.rand.org/pubs/research_reports/RR512.html.7. R. Ellickson, Order Without Law (Harvard Univ. Press,1991).8. A. K. Rai, Regulating scientific research: Intellectualproperty rights and the norms of science. Northwest Univ.Law Rev. 94, 77–152 (1999).Acknowledgments: We thank J. Wilbanks for his idea ofusing a trust mechanism and for fruitful discussions. Theopen science trust concept was developed as part of a course(K.A., R.C., A.E., and Y.L.) at the Faculty of Law, University ofToronto. Structural Genomics Consortium is a registeredcharity (#1097737) that receives funds from AbbVie; BayerPharma AG; the Bill and Melinda Gates Foundation;Boehringer Ingelheim; the Eshelman Institute for Innovation;Genome Canada; the Innovative Medicines Initiative(European Union/European Federation of PharmaceuticalIndustries and Associations) [Unrestricted Leveraging ofTargets for Research Advancement and Drug Discovery(ULTRA-DD) grant no. 115766]; Janssen; Merck & Co.; NovartisPharma AG; the Ontario Ministry of Research, Innovation andScience; Pfizer; the São Paulo Research Foundation FAPESP;Takeda; and Wellcome Trust.10.1126/scitranslmed.aai9055Citation: A. Edwards, M. Morgan, A. Al Chawaf, K. Andrusiak,R. Charney, Z. Cynader, A. ElDessouki, Y. Lee, A. Moeser,S. Stern, W. J. Zuercher, A trust approach for sharing researchreagents. Sci. Transl. Med. 9, eaai9055 (2017). NIV3 of 3ERSITY OF N. CAROLINA - CHAPEL HILL on August 16, 2019A trust approach for sharing research reagentsYunjeong Lee, Andrew Moeser, Simon Stern and William J. ZuercherAled Edwards, Max Morgan, Arij Al Chawaf, Kerry Andrusiak, Rachel Charney, Zarya Cynader, Ahmed ElDessouki,DOI: 10.1126/scitranslmed.aai9055, eaai9055.9Sci Transl Med ARTICLE TOOLS http://stm.sciencemag.org/content/9/392/eaai9055CONTENTRELATED http://stm.sciencemag.org/content/scitransmed/10/438/eaaq1787.fullREFERENCEShttp://stm.sciencemag.org/content/9/392/eaai9055#BIBLThis article cites 5 articles, 1 of which you can access for freePERMISSIONS http://www.sciencemag.org/help/reprints-and-permissionsTerms of ServiceUse of this article is subject to the  is a registered trademark of AAAS.Science Translational Medicinetitle licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. TheScience, 1200 New York Avenue NW, Washington, DC 20005. 2017 © The Authors, some rights reserved; exclusive (ISSN 1946-6242) is published by the American Association for the Advancement ofScience Translational Medicine  at UNIVERSITY OF N. CAROLINA - CHAPEL HILL on August 16, 2019http://stm.sciencemag.org/Downloaded from 

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A trust approach for sharing research reagents

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