Open Source Drug Discovery for Malaria Meeting - February 2012 - Why?



In August 2011 my lab started an open source drug discovery for malaria project. We’ve been a) very excited about this idea, and b) very busy getting things started. It’s an unusual project, exciting not only because we might be able to change the world, but because it’s not clear how we might do it. To me, that’s the definition of good research – you not only don’t know whether it’s going to work, but you don’t even know how to go about doing it.
We had previously found the experience of open science exhilarating, in that the free sharing of all our data and ideas had accelerated a different research project. With new funding for open science we were able to start on drug discovery. Now there has been an Indian OSDD effort that has to date focussed primarily on TB bioinformatics, and who are now moving towards drug discovery (in TB and malaria about which more later). There is the newly-announced Transparency Life Sciences, and Cinderella Therapeutics who are making moves to open up the process of clinical development of compounds. There’s the broad biology-data perspective being championed so effectively by Sage. These are all wonderful, wonderful developments – I hope we are the start, together, of a very significant shift not only in drug development but generally in how we do things as human beings. But I’d felt there was still no basic project in open source drug discovery – something that put medchem and open source together to see what happened, and which started very much from the ground up – making molecules and getting people involved in something specific as a kernel. Tim Wells at the Medicines for Malaria Venture agreed, and we got going in August. We then received [MMV+Aussie Government] funding to 2015. To read what’s going on stay tuned to The Synaptic Leap, G+, OWW and Twitter since things are happening fast and we seriously need people to add momentum.
Over the course of 2011, when describing this project to people, no matter who it was, I would get very high levels of engagement. People wanted to know what osdd was, how it could possibly work, who would pay for it, what happens to intellectual property – a long list of questions. I had answers for some, not for others. I decided it would be a good idea to have a meeting, and one that had a loose agenda, since I have completely converted to unconferences after realising how stale regular conferences can be. I asked Sydney Uni for some money, which they gave me (thank you DVC International for the IPDF scheme), and I started setting up a one-day meeting on open source drug discovery for malaria – to ask in the most general sense whether it can be done. I asked a broad range of people to come and talk about what they thought was interesting. This really is the key to a meeting – you organise coffee, identify good people and say to them “Tell me what’s interesting.”
We met in Sydney on February 24th 2012 and had a fascinating day, then sunset beers in Glebe and dinner. The day was streamed live online. All the talks were recorded. We’re now posting them on YouTube and will annotate them to highlight key points - the links will appear below. If you’ve comments or suggestions please don’t hesitate to write on the relevant posts or on the original YouTube pages. I hope the talks are a way of focussing discussion on the most significant ideas.
The arguments about whether osdd is possible are surprising and astonishing. Not because they are radical, but because osdd is so simple, at heart. Of course as things currently stand osdd is extraordinarily difficult, which is why we’re doing what we’re doing and need people to join. Perhaps the most astonishing thing to realise is that patentless drug discovery has already been done, and is to some extent how things were done before the modern (post-war) conception of the big drug company. I had heard of the polio vaccine and penicillin stories a couple of days before at the AAAS meeting in Vancouver at a talk by Robert Cook-Deegan. Luigi Palombi told the story at the Sydney meeting. If you don’t know about this, or you think that patents are needed for drug discovery, do listen. It’s important to have a Healthy Disregard for the Impossible, but it’s a lot easier when you realise that the “impossible” was actually done a long time ago.
(A shout out to Paul Willis at MMV for coming to the meeting and being our pillar of support. Thanks too to all the amazing help setting up this meeting from my Axis of Open students Paul Ylioja, Kat Badiola, Murray Robertson and Jimmy Cronshaw)

Open Source Drug Discovery for Malaria Meeting - Opening Comments



Opening remarks at the Open Source Drug Discovery for Malaria meeting at The University of Sydney, February 24th 2012. Speaker is Dr Mat Todd, The University of Sydney.

a) The question to address is whether we can we do open drug discovery collaboratively, without patents?
b) This is a very different way of doing things, and therefore interesting in itself.
c) The shift of a lab book on a desk to one on the web is a basic one, but powerful because the internet allows unrestricted collaboration.
d) Open projects have no ownership, unlike the way we do science currently
e) Open projects have fluid composition and leadership
f) Sponsorship for this meeting came from the International Program Development Fund, The University of Sydney and the Sydney osdd project funding from the Medicines for Malaria Venture
g) Diverse participants in the meeting include Saman Habib from the OSDDm project based in India

Open Source Drug Discovery for Malaria Meeting - Session 1, Part 1, Mary O'Kane



Welcome address at the Open Source Drug Discovery for Malaria meeting at The University of Sydney, February 24th 2012. Speaker is Professor Mary O'Kane, Chief Scientist and Engineer, New South Wales, Australia.

Summary: O’Kane passionate about openness in science. It is important that we try to discover new ways of doing research. There have been important moves in recent years in open innovation (e.g. prizes for the solution of big problems). Open science is different since everything is shared. Australian productivity might benefit from these new ideas, and is already investing in key infrastructure projects to make it happen.


1) Professor O’Kane has been passionate about openness in science for a while. Inspired by delegate Richard Jefferson’s work (e.g. Cambia), and the impact that open access to data can have on government. Mentions GIPA (Government Information (Public Access) Act 2009), which allows the public broad access to government data by default


2) Open science for malaria is important for its social and economic impact.


3) Professor O’Kane is on the Board (and is currently, Chair) of Development Gateway (Washington, Brussels) which pushes for open source software for transparency in the developing world and tries to deal with the issue of how we get through barrier of software patents. One product is Zunia – about knowledge exchange via an open platform. Is there is a potential overlap with open source drug discovery?


4) Discussions at this meeting are part of wider question about how we do research. Open innovation and open science are different, but related. DARPA in US – using competition and teams to solve big problems. Produced the microwave oven and the internet (really?). Google Translate was apparently a three-time DARPA project; when the eventual winner was declared Google employed the whole team! Most recently ARPA-E was established in the field of energy. Works with teams for solving problems.


5) Kaggle in Australia works in this way, with data science. The NSW government used it for Sydney's M4 freeway - wanted algorithm that predicts travel times. They supplied 18 months of data and offered $10K as a prize. The produced 364 proposals over 6 weeks, and the teams could see what the other team were doing (very interesting if that’s the case). Won by someone in the US, who generated an algorithm that would have cost the government $1M to build themselves. Science Exchange works by allowing people to subcontract research. There are commercial ventures such as Innocentive and Nine-Sigma.


6) Open science is different – since one shares everything. Science commons, creative commons, neurocommons are related to this. All part of exciting new ways of doing things. Innovation like this is particularly important for Australia, which has a good economy but has in recent years no productivity growth. Open science might boost productivity and improve how Australia works with other countries.


7) Open science needs significant new infrastructure for the management of big data. A mixture of human and automated platforms are needed. NICTA in Australia is key to this, and there should be interactions with this group. Intersect and ANDS also important components. We must seek ways of building eResearch platforms to support open science.


8) The University of Sydney has another resource – Michael Spence, the VC, who was very much in the open commons area in his former life.


Open Source Drug Discovery for Malaria Meeting - Session 1, Part 2, Mary Moran



Part of the first session at the Open Source Drug Discovery for Malaria meeting at The University of Sydney, February 24th 2012. Speaker is Dr Mary Moran, Policy Cures.




1) Patents have big benefits but also big drawbacks. The monopoly a patent brings is useful for generating money for R&D investment. That companies see this as attractive has the knock-on that governments don’t have to pay for R&D, and so companies (rather than governments) take on the risk. The downside of the commercial/patent route is that control of the research agenda is set by the people paying for the research (companies and their shareholders). This means there is little incentive for collaboration.


2) (02:50) However, this patent situation doesn’t apply in NTD research since there is no market because there’s no profit margin; i.e. don’t have the benefits or drawbacks. IP in this area is a “ghost”: not a source of money or an incentive. Companies are more happy about giving IP away that is commercially worthless, and we are seeing this happening more and more in NTD research. e.g. WIPO has a database of available IP for NTDs. Patent pools are becoming more common. Screening in collaboration with companies is getting better/easier in the sense of being more collaborative and hence faster.


3) (05:50) Excluding NIH funding, about 40% of R&D in NTDs is collaborative via Product Development Partnerships (becoming the norm). Not open source but still collaborative on same IP, i.e. small teams, working internationally. e.g. GSK – Tres Cantos as the example (very relevant to this discussion).


4) (07:00) The bad thing about NTD R&D IP being worthless: it’s difficult to fund the work. So the question is can we capitalise on the fact that the patents are worthless? $3 Bn a year now put into making NTD products, all of which is raised outside the market. The money comes from governments ($2 Bn), philanthropists ($0.5 Bn, mainly Gates) and companies ($0.5 Bn). Half a billion of the total goes to malaria product development, and of that 200-300 million a year is invested in malaria drugs. That’s for development of new products (R&D funding) up to the point of registration. (Detailed information is available via Policy Cures G-Finder reports.)

Question from Stuart Ralph at 10 min concerns whether the money discussed is for discovery or late-stage development: [audio unclear]

There have been 300 new NTD products in the development pipeline since 2000, 20 registered, 23 in final stages of trials. Of those, 7 new malaria drugs were registered, 5 of which are “useful”.


5) (11:30) Generally there has been an important shift in mindset about the issue of social responsibility – that NTDs are a public problem arising from a market failure. Companies can contribute, but NTDs are not at heart their problem. Australia puts in less money to product development for NTDs, less than any other “investor” country. Stuart Ralph Question (audio slightly unclear) (12:50): What’s the distinction between basic R&D and product development for the investment numbers. Moran – no distinction, grouped together in this analysis (discovery through to registration). There has recently been a review of Australian funding of NTD R&D, with the recommendation being that e.g. AusAID needs to start funding this area. Typically money has come from overseas to fund NTD R&D in Australia.


6) (14:00) Not having patents gives some freedom: funders can control the whole process. The research is usually done in a not-for-profit way, but the funder takes over the risk. The great benefit: increased collaboration. But the cost savings are quite minor. Discovery is cheap, but has a significant failure rate. The open source impact would be to: i) reduce failure rates by ii) providing better ideas up front and faster through sharing data. Though this is good, it is not a big saving because the R&D is inherently quite cheap. Preclinical research is more expensive, but the open source impact here is less, since you at this stage one needs to share work (rather than data) which is harder and there is less to gained from parallelization, and the work needs to be done in any case. Clinical trials for NTDs (costing e.g. $15-20 M) have high failure rates (3 in 4 early on, then 1 in 4 later). Governments are particularly uneasy about failure rates in drug discovery. Can open source make this more efficient? So open source the easiest to apply in the NTD area because IP is not an issue, and needs to be done. But it also has the least additional benefit because people are already collaborating. But it’s a pilot for the big question for the future: application of open source to commercial areas, which is more difficult, but potentially more impactful. Companies know they can’t keep doing things as they currently are. Keeping the process open as long as possible would reduce cost and risk. NTD R&D is the testing ground for this.


[Questions 21-22 minutes have audio issues. One from Hazel Moir about percentage of funding going to Phase III. One from Stuart Ralph is unclear.]


Not publishing data is a problem in the field. Policy Cures releases their G-Finder info freely, and they receive a lot feedback on that. Efficient. Avoids duplication of effort.


7) (23:50) Question from Mat Todd: [problem with audio] The basic impact of open source in for-profit areas: with open release of data, and with many more eyeballs on the problem, people can spot problems with data earlier on, which helps to reduce time wasted.

Moran: agrees, that if you have more people looking at things, you will improve the work, particularly because there will be critical eyes. As she says “When you’re looking at your own baby it’s always beautiful”. Drug discovery is still fundamentally a risky field, even when the molecules look great late in the process. Early failure saves money.


8) (26:28) Question from Hazel Moir (remote) about US orphan drugs act. [Audio problem] Moran: Orphan drugs are not commercially interesting, so market monopolies are of no use. There is a possibility of reciprocal orphan drug arrangements – for e.g. malaria and TB. But the problem with NTDs, is that nobody in the developed world really has them.


9) (28:50) Question from Paul Willis [Audio Problem]. Moran: Infectious disease is easier to make drugs for because there’s an endpoint. Not so for other problems like high blood pressure. Prior to 2000 there was very little research into drugs for NTDs. So we don’t really know attrition rates yet for the most recent work in the area.


10) (31:40) Richard Jefferson Q: Why are we so obsessed with drugs? The US solved many of these diseases with public health interventions. Why aren’t we focussed on those? Moran: Not sure. Drugs are simple. People reach for tablets/vaccines rather than intervention. Jefferson: Are we doing this because we’re too comfortable with the process? Whereas we need to be honest about whether the research is going to give the desired outcome. Moran: one still feels the strong need to do something proactive when you’re doing the public health R&D. Drugs can do that. Jefferson: What’s the timeline of the two approaches? Say we have a hugely promising lead in the lab. What’s the timeline for that to become a viable treatment vs. an intervention timeline e.g. bednets. Moran: It doesn’t have to be an either/or debate. Todd: public health challenges are daunting, e.g. for schisto, where there is no equivalent of bednets because the parasite is in fresh water, so the availability of a drug allows us to do a lot in the meantime.

Open Source Drug Discovery for Malaria Meeting - Session 1, Part 3, Luigi Palombi



Part of the first session at the Open Source Drug Discovery for Malaria meeting at The University of Sydney, February 24th 2012. Speaker is Dr Luigi Palombi, ANU.




  1. The patent system. There is much mythology about the patent system, mainly that it’s needed for a) drug development and b) innovation. Reality is: not necessarily the case.


  1. (01:29) What happened before the patents system? 1900 was approximate date of birth of patent system, 1883 for the UK. German national patent law passed around 1877. WIPO didn’t exist before 1900. The needs of the people (rather than patents) motivated people to develop medicines. Switzerland didn’t have a patent law until 1907. Novartis and Roche began before the patent system. Germany: 1969 changed law to allow patents on pharmaceutical substances. In most of the EU it wasn’t possible to patent a drug until 1978 when European Patent Convention came into effect. In England – 1919-1949 patents were prohibited on pharmaceutical substances. Yet we have modern medicines.


  1. (4:00) Penicillin was developed without a patent. 1927 - Fleming notes a bacterium-killing substance. Florey later (1938) noted this observation and asked How to turn this observation into a medicine? The team worked in Oxford 1938-1941 without much funding to develop the drug for humans. This was a huge breakthrough for the war effort. The British government found it hard to convince industry to manufacture the drug. Government built a taxpayer-funded factory for this purpose. There was a patent for fermentation production eventually, but generally this was patentless drug development. Perhaps the patent system is applicable in certain areas, but modern pharma has become reliant on the patent model. Is it the way to solve the world’s most important diseases?


  1. (8:00) What is open source? An excuse to get around the patent and copyright systems? Grew from software. In drug development – can this work? Should it really be needed? Ought we to have IP over everything in the drug discovery process? There are patents on drugs as well as research tools. There are patents on naturally-occurring biological materials. Ought there to even be patents on these things? The scope of patentable subject matter has grown. It has become more difficult for scientists to share information openly. This has influenced universities.


  1. (10:10) 1980 - Bayh-Dole in the US. There were great examples where Universities were successful with exploiting patents. Stanford University and Cohen/Boyer breakthrough was a successful act of University patenting, prior to B-D. Generally the BD act has failed. Data suggests Unis are not good at promoting their IP. But the perception has grown that Unis need to create IP like a commercial entity. Now Unis are draconian in ways they implement their IP policies. Once the paragons of sharing and learning have joined the mythology of the patent system.


  1. (11:56) For 3 years politicians and Cancer Council Australia and others have been trying to scale back level of patenting – particularly natural biological materials. Draft legislation is that natural substances are not patentable because they are not inventions. Many universties opposed, so did WEHI/Garvan, which are taxpayer-funded institutes. Many individuals also opposed it. Much philanthropic research funding comes with strings. We are creating mandates and barriers to research and therefore trying to invent open source to get round them. Do we need to go back in time?


  1. (15:27) Polio Vaccine. Not patented – Salk said “Could you patent the sun?” Scientists have become part of the problem because they have succumbed to the myth that patents are required for research funding.


  1. (17:00) Question from Nico Adams (CSIRO). Government-funded, but also funded by outcomes from IP protection. How does one go back to management and say that patents are not necessary? Palombi: level of funding of CSIRO has decreased. Governments have become open to the idea that taxpayers money shouldn’t be spent on research. CSIRO is reliant on public money. Solution – eliminate PPP’s and fund research fully. That is a policy/political decision. Military/auto spending is significant. Since 1980 – is it actually producing what was hoped. The BD act has not been a success. Universities are not good at converting IP to income. There should, by now, be data on this, rather than assumptions about effectiveness.


  1. [Audio problem] (22:18) Moran: Yes, we can do R&D without patents. Can you raise money without patents? It is hard to persuade governments to fund R&D. Governments will always pay for everything in the end, ultimately. Governments prefer risk taken by others initially. So given how difficult it is, how else can we raise money to fund research properly?


  1. [Audio quiet] Question from Paul Willis about counterfeiting drugs. (24:35) Drugs of poor quality are a problem, and a difficult issue. Solution is that we require better regulation. Comment from Saman Habib – poor drugs will occur with or without the patent system. Palombi: There is an international anti-counterfeiting trade agreement, but a confusion in the terminology has arisen about counterfeiting vs. patent violations. There was a warning about Avastin from Genentech about counterfeiting. This is not a patent infringement, but is instead criminal behaviour which can be policed, outside the patent system.


  1. [28:10] Online question: How will the Myriad patent case affect the possibility of patenting genetic material. Are isolated (BRCA1) genetic mutations patentable subject matter? Court decision will be interesting, but possibly not very relevant to Aus because there may soon be a redefinition of patentable subject matter after a recommendation from the Australian Law Reform Commission. If that doesn’t happen, then the Myriad case might have an impact on whether natural biological materials can be patented. Australia may pass the Raising the Bar bill, which will introduce a research exemption to the Patents Act, but will not influence the scope of what may be patented. It’s unclear what will, generally, happen after that.

Open Source Drug Discovery for Malaria Meeting - Session 2, Part 1, Richard Jefferson



Part of the second session at the Open Source Drug Discovery for Malaria meeting at The University of Sydney, February 24th 2012. Speaker is Richard Jefferson, Cambia and the Institute of Open Innovation.




  1. set up about 20 years go with the aim of shifting the demographic of problem solving. The tools built were initially scientific – i.e. enabling technologies. This was an academic success but a practical failure. In an innovation system the rate limiting step is conversion of an idea to a solution.
  2. (2:12) The most important science is the science that fails but fails gracefully, since it provokes the most change. Cambia led to a biological open source movement to try to achieve more collaborative approaches. The latest moves are towards destroying information asymmetry, i.e. to de-risk innovation.
  3. (4:39) Innovation cartography. The power of an evidence base for self-interest. The analogy of trade. For trade one needs a map to reduce risk. The story of the Portugese/Spanish dominance of trade, owing to a very substantial investment in cartography. Maps identify risks. The quality of a map depends on the quality of surveying. The monopoly on maps gave rise to low levels of competition between powers. 1596 – a Dutchman was working in Goa, found the entire stock of Portugese maps. Copied them, went back to Netherlands and published them, open access. This gave rise to an explosion of activity, e.g. the founding of both the Dutch and English East India Companies, i.e. the publication of de-risking tools gave rise to huge commercial activity and innovation in ship building, and in associated areas such as insurance. Knowledge space is the key to business in the modern age, rather than moving commodities. The same metaphors apply. To bring the analogy back – those with money employ patent attorneys and business professionals who are gatekeepers to information. The have risks and expenditures. They recoup the expenses by targeting big innovations, not the small. We need a social revolution to democratize innovation.
  4. (12:25) Jefferson therefore built the Patent Lens. A transparent and inclusive innovation system. Patents are not the problem – they are part of the solution, as a great resource of our species’ technical knowledge. Patents are challenging to read, but still valuable. They are information, but not knowledge, which is more the aim of the Lens – how do we improve how we use patents? Solving a problem is like doing a jigsaw. The solution must be: A) Visualizable - Most important part of a jigsaw is the box – which shows the basic idea. B) Comprehensive – a jigsaw contains all the pieces and can be completed. C) Bounded – has corners and edges. D) Standardizable the pieces only come in certain shapes. These make innovation work. Currently we don’t provide these four requirements in many cases by default.
  5. (18:00) Patents are a right to sue, not a right to do. 80-100 million patents exist. They are public documents and a huge resource. To understand them we need survey points. In journalism this is the Who What When Where Why – these apply also to patents and innovation. The Lens added a Which. The front page of a patent typically has all this information. The Lens is a prototype – beta at the moment – but currently has 80 million patents in it.
  6. (21:13) Demonstration of the Patent Lens. Patents can be filtered easily by e.g. jurisdiction. Much of patent language is human-impenetrable. Need to allow automatic understanding of the text, allowing links between patents. Also need to be able to make links between patents and the academic literature.
  7. (26:30) How the lens facilitates collaboration. Can integrate patents with people. Can annotate patents and share them; can generate collections for projects. Can embed analyses in any other pages. Allows using patents to provide data to support assertions (or not).
  8. (29:28) Used this for Gates and malaria. Gates insist on a global access plan – how it’s clear that your work will find its way to the people who need it? Need to show impediments to delivery/partnerships appropriate. Recent appointment at Gates of new head of global development. Lens developed with agile development, here a pharma patent attorney working with software engineers, and this team was asked to develop a patent landscape for malaria vaccines. So currently has all candidates, with relevant patents, and human-enriched information. Is using an old content management system, and will have more tools soon. Cartography analogy again, that people focus on their local area of interest, and the broader map is built in aggregate. Comment made that most patents that could be enforced are not. They are a valuable resource, in aggregate.
  9. (35:44) Lens not yet live, so there will be bugs. Moving to Chinese, Korean and Japanese patents. Working generally with NCBI and Crossref, then want to move to the business literature, i.e. description of legal entities. The overall goal of the Lens is the removal of barriers to other people’s creativity.
  10. (38:10) Two questions from Mat Todd: 1) will the Lens include chemical structure searching? Jefferson: Yes, but technically challenging. Todd: Would be great if the innovation landscape around molecules could be visualized. Second Q: If we work on an antimalarial, and find that it’s a class of compounds covered by a patent, what do we do? Forbidden to research it? Palombi: Research exemption (low audio) but the clause is too narrow, because of the vagueness of the definition of “research” – there is little research not linked to anything commercial. Overall answer is that generally yes you’re allowed to research something that occupies the same area as an existing patent. The onus would be on the company to find us and ask us to stop, but there is so little incentive for them to do that. Patent infringement of this kind would apply to nearly every university. It actually could help the patent holders by making their methodology clearly more robust. The Lens is open source project. Can be licenced and internalised in companies, sure, but in return the community gets a search tool. Hence worth funding.
  11. (43:41) (Audio low) Observation from Palombi that it’s possible in future that infringing patents may become criminalizable, i.e. to ratchet up enforcement.
  12. (44:18) Jefferson demonstrates the Lens’ biological sequence tool. Sequence information listed associated with species, and which have been associated with patents. Valuable genetic resource for building an evidence base for policy.
  13. (47:00) Nico Adams (CSIRO) Chemical search tools have been developed by Peter Murray-Rust’s group. Chemical patents generally are not well-written. A particular problem is the intentional vagueness of chemical structures. Even if a patent can be read, it then needs to be understood. Jefferson: Mention of Surechem’s patent search tool. Many companies don’t need proprietary tools (don’t have resources to make them very good), they need proprietary outcomes (better information). Most companies frustrated by poor patent, poor tools available. “Companies are either doers or selective deniers”. NCBI can’t (at the moment) do things that are too disruptive in this area.
  14. (50:37) Question from Stuart Ralph. Patents generally awful but they do have a structured and limited vocabulary. Hence need natural language processing? Jefferson: Yes. Patent claims need to be translated into human language.
  15. (53:52) Moran, and others, questions (but audio unclear until 55:10). Nico Adams – Document summarization is important/relevant, e.g. Stephen Wam (CSIRO) interested in summarizing claims in science papers.
  16. (56:15) Final question from Luigi Palombi. Current negotiations are happening for the trans-pacific partnership agreement for the pacific rim, re IP. The Lens makes it easier for people to access information and is therefore relevant. People can’t currently get this information through government-funded patent sites. Should get in touch with e.g. DFAT negotiators. Jefferson: Yes, can become involved in these things when the Lens is ready (beyond beta), i.e. only when it’s comprehensive then it can be wedded to policy making. For example it needs to be at the point where it can understand patent claims.