This document provides a summary of a presentation given by Matthew Todd on open science and open source approaches to research and drug discovery. Some key points discussed include: - Natural human behaviors like curiosity and collaboration can lead to extraordinary scholarship such as the discovery of new things through crowdsourcing and open collaboration. - Open access to publications and data maximizes the benefits of research by allowing broad dissemination and reuse of information. However, current policies often emphasize intellectual property protection over openness. - Open source approaches to problems in areas like software and drug discovery can lower barriers to participation and involve more people in solving challenges. - Open source drug discovery projects for malaria have explored several compound series through open online collaboration and data sharing

1. A/Prof Matthew Todd, School of Chemistry, The University of Sydney
mattoddchem
http://intermolecular.wordpress.com/
NSW Chief Scientist Breakfast Series, Sydney, Oct 28th 2015
Matthew Todd

2. The Nerd Drivers
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1) “Wow, that’s amazing” and “No, no, no – just let me do it”
2) “Let me play with that a second”
http://history.sa.gov.au/files/images/media-releases/8810-national-motor-museumlego-comp.jpg, no licence, fair use

3. Natural Human Behaviour…
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http://ichef.bbci.co.uk/news/624/media/images/77162000/png/_77162574_twitch_ipad_allchannels.png;
http://musically.com/wp-content/uploads/2015/07/napster_napster_streaming_service_702027_g2.jpg;

4. …can lead to extraordinary scholarship
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https://en.wikipedia.org/wiki/Star_Wars:_The_Force_Awakens; mashable.com/2012/03/16/encyclopedia-britannica-wikipedia-
infographic

5. …such as the discovery of new things
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https://en.wikipedia.org/wiki/File:Hannys_voorwerp.jpg; https://upload.wikimedia.org/wikipedia/en/8/8b/Foldit.png
Hanny’s Voorwerp Foldit
OED

6. Boost 1: Open Access
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https://www.nhmrc.gov.au/grants-funding/policy/nhmrc-open-access-policy
Can read, can re-use
“To maximise the benefits from research,
publications … must be disseminated as broadly
as possible to allow access by other researchers
and the wider community… NHMRC therefore
requires that any publication arising from NHMRC
supported research must be deposited into an
open access institutional repository and/or made
available in another open access format within a
twelve month period from the date of publication.”
http://s3.amazonaws.com/libapps/customers/1510/images/ieee_infographic.jpg
Industry Access to the Literature, Stewart Lyman, Nature Biotech 2011, 29, 571–572. doi: 10.1038/nbt.1909
(thanks Neil Saunders (https://twitter.com/neilfws/status/658817640400580608), Bill Hooker)
See also http://aoasg.org.au/2015/08/07/aoasg-response-to-australian-government-paper-vision-for-a-science-nation/

7. Boost 2: Open Data
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Power of Re-use
The Human Genome Project cost approximately $4bn, but the release of the data into
the public domain created hundreds of billions in downstream scientific activity
Economic Impact of the Human Genome Project, Battelle Technology Partnership Practice, 2011
Papers from Hubble
Papers published by acquirers of data < papers
published by users of the data
http://archive.stsci.edu/hst/bibliography/pubstat.html;
http://archive.stsci.edu/hst/bibliography/basic_methodology.ht
ml; Thank you Andrew Treloar, ANDS
And
Piwowar HA, Vision TJ. (2013) Data reuse and the open data
citation advantage. PeerJ 1:e175
https://dx.doi.org/10.7717/peerj.175
Gates Foundation Open Access Policy
http://www.gatesfoundation.org/How-We-Work/General-Information/Open-Access-Policy
The Foundation will require that data underlying the published research results be
immediately accessible and open.

8. Boost 2: Open Data
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Who are the data for?
Houghton, J., Gruen, N. (2014) Open Research Data Report to the Australian National Data Service (ANDS).
November 2014 http://ands.org.au/resource/open-research-data-report.pdf

9. Boost 2: Open Data
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http://en.chessbase.com/Portals/4/files/news/2013/advancedchess02.jpg;
https://tedconfblog.files.wordpress.com/2013/04/watson_the_computer_beats_ken_jennings_and_brad_rutter_at_jeopardy_full-1.jpg;
Nature 427, 247-252, 2004. doi:10.1038/nature02236
Who are the data really for?

10. Boost 2½: Open Innovation
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H. W. Chesbrough, Open Innovation: The new imperative for creating and profiting from technology. Boston: Harvard Business
School Press, 2003 (ISBN 978-1578518371)
A Nebulous Set of Ideas, Some Useful
“Open innovation is a paradigm that assumes that firms can and should use
external ideas as well as internal ideas, and internal and external paths to
market, as the firms look to advance their technology.”

11. Boost 3: Open Source
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A Different Way of Working
http://bit.ly/9Pv119;
http://bit.ly/9VTpqj

12. Boost 3: Open Source
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A $5 Billion Value: Estimating the Total Development Cost of Linux Foundation’s Collaborative Projects, The Linux Foundation Report
2015 (Thanks Bill Hooker (https://twitter.com/sennoma/status/658816532147900416))
https://en.wikipedia.org/wiki/File:Usage_share_of_web_browsers_%28Source_StatCounter%29.svg

13. http://au.mathworks.com/matlabcentral/contest/contests/3/statistics.html
Sometimes Brutal, Frenzied
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14. We Need New Models in Pharma
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Address by WHO Director General Margaret Chan, Regional Committee for Africa, 64th Session, Cotonou,
Republic of Benin, 3rd Nov 2014. http://www.who.int/dg/speeches/2014/regional-committee-africa/en/
Research and Development to Meet Health Needs in Developing Countries: Strengthening Global Financing and
Coordination, Report of the Consultative Expert Working Group on Research and Development: Financing and
Coordination, World Health Organization, 2012, ISBN: 978 92 4 150345 7, http://www.who.int/phi/cewg_report/en/

15. An Industry Facing Challenges
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D. W. Light and J. R. Lexchin, BMJ 2012, 345, e4348. (DOI: 10.1136/bmj.e4348)

16. An Industry Facing Challenges
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https://www.opensecrets.org/lobby/indusclient.php?id=H04

17. http://www3.imperial.ac.uk/schisto; http://bit.ly/9azFHv
Open Source vs. Pharma?
N
N
O
O
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18. Trouble with Praziquantel
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N
HCN
Experientia 1977, 33, 1036
N
N
O
O
H
(R)-enantiomer
active
N
N
O
O
H
(S)-enantiomer
inactive, bitter
10 ¢ per gram
N
O
HN
O
O
O
O
c. H2SO4
Tetrahedron 1998, 54, 7395
COST
TIME
BREAKING POINT
THRESHOLD
When confronted with a difficult problem…

19. How #1: Be Open with what you can’t do
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20. H
N
O
N
O
O O
N
O
N
O
H
catalyst
Industrial
Precursor
Praziquantel
How #2: Share the Details
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21. How #3: Involve Everyone
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22. Current Solution
Details of Route: PLoS NTD 2011, 5(9): e1260
Full Description of Project: Nature Chemistry 2011, 3, 745-748
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23. HIT LEAD?
CONVENTIONAL DRUG DISCOVERY
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A
A “born open”
open source approach
to new medicines?

24. Great Starting Open Data
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25. The Experiment: Open Source Malaria
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http://www.thesynapticleap.org/node/343

26. The Four Campaigns So Far
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http://openwetware.org/wiki/OpenSourceMalaria:Compound_Series
Series typically not exhausted - Decision points made to move to another.
Anyone free to employ OSM infrastructure to explore these series
F
H2N
N
O
O
O
F
N
HN
N
O
S
O
N
N
N
S
N
Cl
O
O
N
N
N
S
NH2 S NH2
O
O
N
N
N
N
O
F
F
HN O
Cl
SERIES 1
Potent
Ester problematic
SERIES 1A
Potent
Gametocyte active
Low solubility
SERIES 2
Potent
Duplication with Closed Group
SERIES 3
Potent
Singleton?
SERIES 4
Already investigated in Pharma/CRO
Promising PK
Possible PfATP4 activity
PARKED ONGOING NEW

27. How #4: Lower the Barriers
Open Source Drug Discovery – A Limited Tutorial, Parasitology, 2014, 141, 148–157
ONLINE LAB BOOKS DATA MANAGEMENT OPEN PROJECT MANAGEMENT
ONLINE MEETINGSALERT MECHANISMS @O_S_M
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28. 28/46

29. 29/46

30. 30/46

31. Trust as Transparency
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https://commons.wikimedia.org/wiki/File:HK_TST_Chung_King_%E6%B4%BB%E6%96%B9%E5%95%86%E5%A0%B4_Woodhouse_Japanese_restaurant_Jika_Udon_open_kitchen_window.JPG

32. 32/46
Openness Boosts Research and Education

33. Openness Boosts Publishing
Current
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Paper
Data Treat
Icing
Human Proof
http://ses.library.usyd.edu.au/handle/2123/10461

34. Openness Boosts Longevity
Current
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1. Data
2. Project
3. The what-would-
we-have-done-next

35. But… Secrecy
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We are obliged to be secretive
The University of Sydney (Intellectual Property) Rule 2002 (as amended),
http://sydney.edu.au/policies/showdoc.aspx?recnum=PDOC2011/108
“staff have responsibilities in relation to intellectual property protection
including … the prevention of premature public disclosure of research
results prior to obtaining intellectual property protection”

36. Patents Slow Basic Research
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“British and French synthetic dye firms that initially dominated the synthetic
dye industry because of their patent positions but later lost their leadership
positions are important cases in point. It appears that these firms failed to
develop superior capabilities in production, marketing and management
precisely because patents initially sheltered them from competition. German
and Swiss firms, on the other hand, could not file for patents in their home
markets and only those firms that developed superior capabilities survived
the competitive home market.”
The Case Against Patents, M. Boldrin and D. K. Levine, J. Econ.
Perspectives 2013, 27, 3-22; Against Intellectual Monopoly, CUP, 2008
“…evidence that Celera’s IP led to reductions in subsequent scientific
research and product development on the order of 20–30 percent”
Intellectual Property Rights and Innovation: Evidence from the Human
Genome, H. L. Williams, J. Political Economy 2013, 121, 1-27.

37. Financial Value of Tech Transfer
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http://www.theguardian.com/technology/2015/oct/17/apple-ordered-to-pay-234m-to-university-for-infringing-patent
130 universities did not generate enough licensing income in 2012 to cover the wages of
their technology transfer staff and the legal costs for the patents they file. What is more,
with 84% universities operating technology transfer in the red, 2012 was a good year
because over the last 20 years, on average, 87% did not break even.
W. D. Valdivia, Center for Technology Innovation at Brookings, November 2013.
http://www.brookings.edu/research/papers/2013/11/university-start-ups-technology-transfer-valdivia

38. The Trans Pacific Partnership
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http://www.abc.net.au/news/2015-10-06/pacific-nation-ministers-negotiators-lock-in-tpp-trade-deal/6829368

39. Public Sector as Innovator
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[Similarly to venture capital, which] entered industries like biotechnology only after the
State had done the messy groundwork, the genius and “foolishness” of Steve Jobs led to
massive profits and success , largely because Apple was able to ride the wave of massive
State investments in the “revolutionary” technologies that underpinned the iPhone and
iPad: the Internet, GPS, touch-screen displays and communication technologies. Without
these publicly funded technologies, there would have been no wave to foolishly surf.
M. Mazzucato, The Entrepreneurial State, Chapter 5, ISBN 978-0-85728-252-1
Public-private partnership depositing data from
high risk projects into public domain for potential
exploitation by others
T. Spangenberg, J. N. Burrows, P. Kowalczyk, S. McDonald, T. N. C.
Wells and P. Willis, PLOS ONE 2013, 8(6): e62906. DOI:
10.1371/journal.pone.0062906
MMV Malaria and Pathogen Box Projects
Providing samples of bioactive compounds on
condition data are made available

40. So … What Do we Do?
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Open Closed
Caution/foresight
Financial clarity
Better Research
Conditions are Tough: Set up a Competition of Models

41. Other Financial Models in Pharma
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Advance Market Commitments &
International Financing Facilities
Independent Mobilization of Donor Funds
Levy on Airline Tickets
R. Atun, F. M. Knaul, Y. Akachi and J. Frenk, Lancet 2012, 380, 2044–2049

42. Other Financial Models in Pharma II
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Priority Review Vouchers
A. Banerjee, A. Hollis and T. Pogge,
Lancet 2010, 375, 166–169. DOI:
10.1016/S0140-6736(09)61296-4
J.-M. Fernandez, R. M. Stein and A. W. Lo, Nature Biotech. 2012, 30,
964–975. DOI: 10.1038/nbt.2374
P. Doshi, BMJ 2014, 349:g4665. DOI: 10.1136/bmj.g4665
Prizes
Crowdfunding

43. Patents Aren’t Necessary
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Penicillin, The Polio Vaccine
ASAQ/Coarsucam
Fexinidazole
Bompart F, Kiechel JR, Sebbag R, Pecoul B (2011) Innovative Public-Private Partnerships to Maximize the Delivery of Anti-malarial
Medicines: Lessons Learned from the ASAQ Winthrop Experience. Malaria Journal 10:143. doi:10.1186/1475-2875-10-143
Torreele E, Bourdin Trunz B, Tweats D, Kaiser M, Brun R, Mazué G, et al. (2010) Fexinidazole – A New Oral Nitroimidazole Drug
Candidate Entering Clinical Development for the Treatment of Sleeping Sickness. PLoS Negl Trop Dis 4(12): e923.
doi:10.1371/journal.pntd.0000923

44. Open Source Pharma?
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WHO/TDR meeting, Geneva, Sept 2013
OSP1
Rockefeller Bellagio, Italy, July 2014
Academia, Industry, NGO, Funders
@OSPinfo, www.opensourcepharma.net
OSP2
Castle Rauischholzhausen, Germany
Sept 1st-3rd, 2015
Minutes: http://tinyurl.com/OSP2Final
Open Source Pharma Foundation
created with US$3M funding from
Tata Trusts, Sept 2015

45. Best use of the MRFF
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46. Sydney: Michael Woelfe, Paul Ylioja, Murray Robertson, Alice Williamson, Kat Badiola, Jimmy Cronshaw, Zoe Hungerford,
Laura White, Clara Chen, Angela Butera, Matin Dean, Althea Tsang, Jo Ubels, Tom MacDonald, Matt Tarnowski, Peter
Turner, Carmen Tran, Inga Topolnicki WHO/TDR: Piero Olliaro Syncom B.V.: Jean-Paul Seerden MMV: Tim Wells, Paul
Willis, Jeremy Burrows GSK: Javier Gamo, Felix Calderon, Lluis Ballell, Julia Castro-Pichel Southampton: Jeremy Frey
and team ChEMBL: John Overington, Iain Wallace, George Papadatos ANU: Kiaran Kirk, Adele Lehane, Adelaide Dennis
OSDD India: Sanjay Batra, Soumya Bhattacharyya Eskitis: Vicky Avery, Sandra Duffy, Sabine Fletcher Monash: Sue
Charman, Karen White Melbourne: Stuart Ralph, James Pham Basel: Sergio Wittlin Edinburgh: Patrick Thompson,
Eduvie Omene, Devon Scott Pfizer: Scott Obach, Christine Orozco Lawrence University: Stefan Debbert Karolinska
Institute: Sabin Llona-Minguez, Thomas Helleday University of British Columbia: Corey Nislow, Marinella Gebbia, Anna
Lee AstraZeneca: Asclepia: Frederick DeRoose UCSD: Stephan Meister St Jude’s Hospital: Kip Guy, Julie Clark Other
Online: Chris Southan, Jonathan Baell, Chris Swain and others; OSP/OSPF: Jaykumar Menon, Peter Kolb, Bernard Munos,
Els Torreele, John Wilbanks, John McKew, Tomasz Sablinski, Dimitrios Tzalis, Rockefeller Foundation, House of Pharma,
Tata Trusts
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Thank You

48. Boost 2: Open Data
Gates Foundation Open Access Policy
http://www.gatesfoundation.org/How-We-Work/General-Information/Open-Access-Policy
Can play with, can re-use
The Foundation will require that data underlying the published research results be
immediately accessible and open.
Feynman believed that scientists should constantly remind themselves of their biases.
“The first principle” of being a good researcher, according to Feynman, “is that you must
not fool yourself, and you are the easiest person to fool.”
Alex Holcombe, Science is Best when the Data is an Open Book, Conversation, Oct 2015
https://theconversation.com/science-is-best-when-the-data-is-an-open-book-49147
http://www.ands.org.au/datamanagement/funding.html
3.1 The ARC does not mandate open data. However, researchers are encouraged to
consider the ways in which they can best manage, store, disseminate and re-use data
generated through ARC-funded research.

49. Reproducibility
If we fund research, the research must be sound
Nature, 27th August 2015. 10.1038/nature.2015.18248
C. G. Begley and L. M. Ellis, Nature 2012, 483, 531–533. DOI: 10.1038/483531a

50. Other Models of Research
Patent pooling
Non-profit Biotech
Closed, sometimes virtual,
consortia
Virtual Pharma

51. Wall Street Journal
May 26th 2010
Sharing Materials is Crucial
T. Spangenberg, J. N. Burrows, P. Kowalczyk, S. McDonald, T. N. C.
Wells and P. Willis, PLOS ONE 2013, 8(6): e62906. DOI:
10.1371/journal.pone.0062906
http://pathogenbox.org/
http://www.thesgc.org/chemical-probes
A. M. Edwards, C. Bountra, D. J. Kerr and T.
M. Willson, Nature Chem. Biol. 2009, 5, 436–
440. DOI: 10.1038/nchembio0709-436