There is an argument that says we should not be making simple compounds in academic research labs, but rather using specialist services to make molecules with which we then do interesting science. There is a lot of truth to that, particularly with medchem projects involving structures that are simple, or for which there is synthetic precedent. We’re making compounds in my lab as part of the open source drug discovery for malaria project because we’re trying to drive a unique way of doing things in the open and show that that works, but if everyone started doing open source drug discovery, and it became the standard way of doing things, I wonder if the process would be more efficient if we used a network of CROs, or even a set of super-labs specializing in synthesis (a proposal I’m thinking about, but I can’t decide whether it should be government- or industry funded). I think Elizabeth Iorns of Science Exchange has mentioned this idea too.
The potential for CROs to make an impact on open projects is great. This is because an open source project consists of a nimble network. In regular research projects, funded by government grants, one will typically define the project structure at the start, cost up the resources, and then carry out that research in a manner that is closely related to the proposal. Naturally there will be variations in science and approach, but there are usually not huge variations in the structure of the team. Indeed, if there is no clear plan of how to carry out the research at the outset, that can be viewed dimly by referees. If the structure of the project changes dramatically during the funding period that can often require explicit reasons in end-of-project reports. There is thus some incentive in keeping the project as-designed. There may also be professional or emotional ties that mean a team is kept together even if it turns out it’s not the best team for the job.
In contrast open source projects demand a nimbleness – that people get involved if needed, and that the required people may not be those defined in advance. I have found this challenging to explain in grant proposals, where I have tended to define project participants at the outset, and mentioned that the team will adapt and change in a process that is not fully controlled. I try not to highlight it too much, even though I know the ever-shifting project structure is one of the great novelties and strengths.
So open projects are strong because of a loose set of transient connections. Interestingly this kind of network was recently shown to result in more cooperative behavior than networks with strong, more permanent connections between members. It’s a model, but an interesting one that to some extent mirrors what we’ve seen in our open science projects.
Nimble projects can use small inputs from a number of people if needed, and those people, once they have contributed, have no obligation to continue to contribute. An open structure relies on enthusiasm and available resources and is very good at accepting small components from many people. This kind of project takes much more coordination, and is more complex, but should ultimately be more efficient provided there is strong, open management.
So if we want to evaluate a series of compounds in a medchem program, for example, where the compounds are not necessarily methyl-futile analogs, but consist of different structures that may require different kinds of chemistry, it makes more sense to break up the work involved, and have several labs make a small number of compounds in parallel. It makes particular sense if there is a lab somewhere with expertise in the synthesis of a particular structure class, for example, who might be able to make that kind of structure quickly.
CROs are set up perfectly for this, since they could make a single compound for a project during a short (1-2 week) downtime for a lab member, and then once that compound has been made they are not required to be involved any further. Rather like a bit torrent client that uses spare capacity in short bursts.
The CRO marketplace is crowded and, I’m guessing, working with tight profit margins. Naturally companies are under pressure to attend to their core business. So why would a CRO want to contribute to an open source project? Several reasons:
1) PR argument 1: If the project is philanthropic, the company gains a positive public image for contributing to the solution of that problem.
2) PR argument 2: By performing the work in the open, where all data are shared in real time, a company can demonstrate its technical prowess, i.e. onlookers can see how fast a company can work, and the quality of the work in detail and in a real case scenario. Big pharma could observe the quality before contracting the company for new work.
3) Employee satisfaction I: I believe (without data) that people are people and that employees working on a philanthropic project gain professional satisfaction from doing so.
4) Employee satisfaction II: Scientists like to solve problems, and a challenge in parallel to one’s paid work, particularly if part of a team effort, is satisfying. Those taking part will likely secure publications.
5) Exploitation of Unavoidable Downtime: Even an efficiently-run CRO will have periods of a week or so where an employee is not fully occupied. That spare time can be put to good use with the kinds of small contributions needed by open projects.
6) Philosophical Agility: If a marketplace is tough, an edge is given to those companies who can distinguish themselves. Taking part in an open research project, which is an unusual thing to do, demonstrates a company is happy to think laterally and engage with ideas outside the comfort zone of their competitors.
These arguments mirror those that I presume operate in what is an excellent model for what I’m proposing – the pro bono work performed by law firms. This is a major component of the legal profession. Now in many cases the big pro bono cases are those taken on by the big firms, and the analogous situation is the fantastic work that many of the big pharma companies are doing in philanthropic work for neglected tropical diseases – impressive and little-known by the public. One might argue that the CRO sector, which is more under pressure, cannot afford to contribute this way. I disagree, and return to the idea that an open project can be advanced by small contributions, appropriately coordinated. Rather than a CRO being locked into a collaborative arrangement for a long time, a CRO could be engaged in an open project (to make a molecule or acquire some data) for days or weeks before moving on to something more aligned with core business.
What’s needed? Open data and an open research method will allow people to find and see what a project needs in a very responsive manner. But it’s imperfect since we may not search for the right thing, or the project participants may not record/coordinate their data in a way that is easily found. Perhaps instead we need a Clearing House for Contributions to Research. A place where people can say what work they need doing, and the clearing house tries to find companies who can do that work. Such a thing exists in law – PILCH – that matches those seeking pro bono work with those companies best able to provide that work. This mirrors the idea of the Molecular Craigslist I floated – where people could upload structures of molecules they need, and people can bid to provide those, i.e. needs-driven, not supplier-driven.
Science Exchange and Assay Depot are like this, but again the process is not open (as far as I know). Thus I can request a service and receive quotes/offers (though to be clear I’ve never tried that) but I suspect the bidding process is not an open market auction-style. I’d like to see an open variant where there is a genuine process of bidding, in case someone wants to provide a molecule or service for free, for example, or in case the open procurement process itself could stimulate interest in contributing to the project. Perhaps Science Exchange and others could have an option to make the matchmaking process open. i.e. I need X, who would like to provide it?
To date I have pitched the idea of contributing to the open malaria project to three CROs. One didn’t reply. One said they weren’t interested (but from the response I suspect my request was not well understood) and one said the following, to paraphrase: “Thank you for your mail. This request is very innovative. We are not interested in taking part because no other CRO is currently taking part”. I found this last reply quite interesting because the logic to me was the reverse of what I had expected. To me, it would have been a plus that nobody else was doing open source work, since were I to take part that would distinguish my company from all the others.
So we’re going to be sending out more requests to CROs to make molecules as part of the osdd malaria project – at the time of writing there are several that are still needed. If my arguments above are right, there should be interest from the CRO sector. The question is how best to engage with that sector.