1. “Open and Collaborative” Research: A New Model for Biomedicine Arti K. Rai Professor, Duke Law School January 11, 2005 rai@law.duke.edu

2. Biology Research: A Simplified History Until late 1970s, molecular biology not applicable commercially Until late 1970s, molecular biology not applicable commercially Few IPRs Few IPRs But secrecy: fierce competition among small labs for publication priority But secrecy: fierce competition among small labs for publication priority 1966: only 45% of biologists felt comfortable talking outside lab (Walsh & Hong 2003) 1966: only 45% of biologists felt comfortable talking outside lab (Walsh & Hong 2003) Higher percentage than other sciences (cf. Merton – communal production in prestige economy should lead to great openness) Higher percentage than other sciences (cf. Merton – communal production in prestige economy should lead to great openness)

3. The Move Towards Proprietary Rights in Research Molecular biology becomes commercially appealing Molecular biology becomes commercially appealing Bayh-Dole encourages university patenting and exclusive licensing for purposes of commercialization Bayh-Dole encourages university patenting and exclusive licensing for purposes of commercialization Court of Appeals for the Federal Circuit Court of Appeals for the Federal Circuit

4. University Biotechnology Patents: 1980-2000

5. Current Complaints Some broad patents, exclusive licensing Some broad patents, exclusive licensing Possible “thickets” (Heller & Eisenberg 1998) Possible “thickets” (Heller & Eisenberg 1998) Increasing secrecy? (Campbell et al. 2002) Increasing secrecy? (Campbell et al. 2002) NIH, NRC emphasize access NIH, NRC emphasize access

6. Beyond Access:”Open and Collaborative” Production Disavows exclusionary IPRs and focus on individual small lab Disavows exclusionary IPRs and focus on individual small lab Influenced by model of OS software (took root when CS/cyberinfrastructure migrated to biology) Influenced by model of OS software (took root when CS/cyberinfrastructure migrated to biology) Another foil: high energy physics Another foil: high energy physics

7. OS Production of Software: History Some roots in academic/Mertonian modes of production Some roots in academic/Mertonian modes of production But always had explicit mechanisms for information integration But always had explicit mechanisms for information integration

8. OS Software Now Heterogeneous: 80,000 or so projects Heterogeneous: 80,000 or so projects Most OS projects don’t occur in academic sector (intrinsic and extrinsic motivations well beyond Merton) Most OS projects don’t occur in academic sector (intrinsic and extrinsic motivations well beyond Merton) Commercial firms make profits on complementary services Commercial firms make profits on complementary services But biomedical research inspired by OS model often occurs in academia (though more hierarchy/integration than Merton) But biomedical research inspired by OS model often occurs in academia (though more hierarchy/integration than Merton)

9. Categories of OC Biomed Research Highly modular: open source bioinformatics software Highly modular: open source bioinformatics software Modular: genomic databases Modular: genomic databases Beyond modular information: wet labs Beyond modular information: wet labs

10. Empirical Project Thus Far Semi-structured interviews of scientists involved in OC work (snowball sampling) Semi-structured interviews of scientists involved in OC work (snowball sampling) Ask corresponding university tech transfer officers about projects Ask corresponding university tech transfer officers about projects Interviewing tech transfer officers of “top” biotech, software patentees and recipients of NIH funding about OS software Interviewing tech transfer officers of “top” biotech, software patentees and recipients of NIH funding about OS software

11. OS Software Projects www.bioinformatics.org (195 projects) www.bioinformatics.org (195 projects) www.bioinformatics.org Most licenses not “plain vanilla” GPL (as contrasted with 72% at Sourceforge) Most licenses not “plain vanilla” GPL (as contrasted with 72% at Sourceforge) Cf. Lerner and Tirole (the scope of Open Source) Cf. Lerner and Tirole (the scope of Open Source)

12. Policies of TTOs Not much software patenting by universities (Drop from 1% to 0.6% of total in period from 1980 to 2000?) Not much software patenting by universities (Drop from 1% to 0.6% of total in period from 1980 to 2000?) Cultural differences: software vs. biology Cultural differences: software vs. biology Some TTOs in midst of formulating policy Some TTOs in midst of formulating policy Others in “don’t ask, don’t tell” mode Others in “don’t ask, don’t tell” mode MIT, Stanford, UT report deference to researchers MIT, Stanford, UT report deference to researchers Cf. University of Washington, Georgia State Cf. University of Washington, Georgia State

13. Genomic Databases Human Genome Database paves way (copyleft vs. public domain) Human Genome Database paves way (copyleft vs. public domain) Better sequencing machines improve modularity Better sequencing machines improve modularity Feb. 2003: principles extended to all genome sequencing projects Feb. 2003: principles extended to all genome sequencing projects Collaborative improvement through DAS Collaborative improvement through DAS Policy imposed on TTOs Policy imposed on TTOs

14. International HapMap Project Aims to catalogue patterns of genotypic variation (“haplotypes”) Aims to catalogue patterns of genotypic variation (“haplotypes”) Achieve association of haplotypes with complex disease Achieve association of haplotypes with complex disease HapMap Data Access Policy: copyleft model (until recently) HapMap Data Access Policy: copyleft model (until recently) Until haplotypes determined and released, access to individual genotype information conditioned on not using it to seek patents on haplotypes Until haplotypes determined and released, access to individual genotype information conditioned on not using it to seek patents on haplotypes

15. “Wet Lab” Biology Work often not modular (in case of AFCS, “vast uncharted territory”) Work often not modular (in case of AFCS, “vast uncharted territory”) Harder to see translation Harder to see translation

16. AFCS 8 labs: 7 “wet labs,” 1 bioinformatics lab 8 labs: 7 “wet labs,” 1 bioinformatics lab “High-throughput” analysis of how cells respond to different chemicals “High-throughput” analysis of how cells respond to different chemicals Labs use same inputs, analyze different types of outputs Labs use same inputs, analyze different types of outputs Much work has gone into standardization of inputs Much work has gone into standardization of inputs But work is still highly interdependent But work is still highly interdependent

17. IPRs and Publication Al Gilman required disavowal of all IPRs Al Gilman required disavowal of all IPRs Reluctance on part of participating TTOs Reluctance on part of participating TTOs Research reports published on Web after limited peer review Research reports published on Web after limited peer review

18. Evaluation: Software Arguments for and against OS software (and public funding thereof) Arguments for and against OS software (and public funding thereof) WMEABAS and transaction costs WMEABAS and transaction costs But modularity itself should reduce such costs somewhat (markets for technology) But modularity itself should reduce such costs somewhat (markets for technology) Need for viral licensing unclear Need for viral licensing unclear Universities won’t get involved unless lots of consulting revenues Universities won’t get involved unless lots of consulting revenues

19. Evaluation: Databases Need for some (significant?) public funding to create database Need for some (significant?) public funding to create database Agency pressure needed Agency pressure needed DAS and transaction cost reduction? DAS and transaction cost reduction? Transaction cost reduction for downstream players (e.g. pharma)? Transaction cost reduction for downstream players (e.g. pharma)? Viral licensing could be problematic Viral licensing could be problematic Shows need for research exemption? Shows need for research exemption?

20. Evaluation: Wet Lab Very significant coordination, funding needed; limits on number of participants Very significant coordination, funding needed; limits on number of participants But systems biology probably require resources of more than one small lab But systems biology probably require resources of more than one small lab Lack of systems biology knowledge may be why drugs are failing Lack of systems biology knowledge may be why drugs are failing Disavowal of future IPRs may substantially reduce transaction costs for collaborations in inchoate areas Disavowal of future IPRs may substantially reduce transaction costs for collaborations in inchoate areas

21. Transaction Cost Problems Complex non-disclosure agreements to prevent information leakage Complex non-disclosure agreements to prevent information leakage Arguments about ownership of future discoveries in inchoate areas Arguments about ownership of future discoveries in inchoate areas Default ownership rules in patent area unattractive Default ownership rules in patent area unattractive But default rules “information forcing,” avoid anticommons; changes could be problematic But default rules “information forcing,” avoid anticommons; changes could be problematic AFCS vs. Cell Migration Consortium AFCS vs. Cell Migration Consortium

22. Viral Licensing, Incentives, and IPRs Viral licensing could be very problematic Viral licensing could be very problematic Insufficient incentives for young data generators? Insufficient incentives for young data generators? Move towards conventional publication? Move towards conventional publication? Should be able to publish based on publicly available data Should be able to publish based on publicly available data Long-term: publish first, peer review later? (arXiv.org model) Long-term: publish first, peer review later? (arXiv.org model) Very hard to get universities to disavow IPRs Very hard to get universities to disavow IPRs

23. Conclusion For modular information, OC may reduce transaction costs to some extent For modular information, OC may reduce transaction costs to some extent For “inchoate” wet lab biology, OC may substantially reduce such costs For “inchoate” wet lab biology, OC may substantially reduce such costs Institutional obstacles in both cases (greater in latter case) Institutional obstacles in both cases (greater in latter case)