Companies and Open Science
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.
bill 5:31 pm on September 25, 2012 Permalink |
I work at a biotech firm not a CRO, but I occasionally contract out work — mosty manufacturing and clinical stuff. From the little I’ve seen, your arguments should carry weight (well, 3 and 4 are less meaningful to the business types). My experience has been that it can take 10-20 attempts to find a good match, so you’re right not to be discouraged after only three. You write well so I probably can’t improve it, but I’d be happy to take a look at your intro email if you like.
mattoddchem 10:53 pm on September 29, 2012 Permalink |
Thanks Bill. I’ve posted the draft email here: http://bit.ly/SVuRqu. If you’ve time to take a look, that’d be great.
Elizabeth Iorns 10:26 pm on September 25, 2012 Permalink |
Very interesting article! We could certainly have an ‘open project’ option – I’ll ask our developers how difficult it would be to implement and get back to you – thanks for the suggestion!
Cameron Neylon 6:53 pm on September 26, 2012 Permalink |
I can see at least one other reason why a CRO would want to contribute (even on a pro or low-bono level) and that is to grow what is potentially a massive market for them at relatively low risk. By creating a larger pool of projects operating in this nimble fashion there is significant potential to grow up a paying market in which researchers purchase their services because its the most cost effective way to get things done. But that market has to be created.
Kevin Lustig 2:16 pm on October 3, 2012 Permalink |
When we started Assay Depot 5 years ago, we thought about setting up a commercial bidding process in much the way you describe. We envisioned that scientists would come to the site, list what they needed and get bids from any interested vendors. Scientists and vendors, however, were less than enthusiastic about the idea. We found that many scientists, particularly from biotech and pharma, did not want to post their requests publicly, where they would be visible to their competitors. Vendors also did not like an open bidding process, in which their prices would be visible to possible competitors.
Our solution was to create a taxonomy of 500 research areas, to identify vendors in all 500 research areas and to make it easy and free for a researcher to reach out privately to two, twenty or two hundred pre-selected vendors at the same time (and ask a question or request a quote). With some simple online tools we’ve built, it’s almost as easy to communicate privately with fifty vendors as with a single vendor. This approach keeps the entire set of conversations private, pleasing both scientists and vendors.
I think your idea of an open matchmaking process for free services and capabilities is a good one. There must be hundreds of academic and industry laboratories that are looking for a collaborator in a certain area or that have excess capacity on an specialized instrument and are willing to use it for a good cause, without compensation or in exchange for in kind services. Looking out a few years, I can even imagine a thriving “research bartering” system that facilitates collaboration and enables global research partnerships for both small and large laboratories in academia and industry.
drgunn 10:38 pm on October 3, 2012 Permalink |
” There must be hundreds of academic and industry laboratories that are looking for a collaborator in a certain area or that have excess capacity on an specialized instrument…”
Isn’t that pretty much what Science Exchange does? They’re focusing on core facilities at universities, but it seems to me like the line between a “official” core facility and a lab that has a specialized instrument and wants to fill excess capacity is a pretty thin line. The whole point of the Reproducibility Initiative they’re leading, which Mendeley is also a part of, is to get some of this excess capacity put to good use. It’s not explicitly philanthropic, but if we can raise some funds, it will be, and anyways creating a collection of replicated high-impact work will help organizations such as patient advocacy groups and disease foundations.
Speaking about open discovery more generally, there are few labs which really are working openly, as you all know, but once we shift the focus of academic achievement away from just getting citations towards a more reuse centered approach, there will be no reason why people don’t work openly. In fact, it will become essential for success.
Kevin Lustig 5:02 pm on October 4, 2012 Permalink |
I believe that we are headed toward a new era of science where we are all “service providers” to one another, an era in which we openly share our unique talents and work closely together in ways almost unimaginable just 10 years ago. That being said, I think it will take some years to get there.
Until the enormous explosion in pharmaceutical research outsourcing over the last ten years, there was a clear division between academic core labs and CROs, which offer services, and research laboratories, which make research breakthroughs. One was clearly subservient to the other. Now that it is possible to obtain any research service imaginable from any university or commercial vendor through applications like Assay Depot (and at least 12 other research service matchmaking sites), the distinction is not so clear. Anyone can now access world-class experts in any research area, and anyone can obtain any research service, provided they have the resources to fund the work. In certain important ways, life science research has become decentralized and democratized.
In this new era of science, research laboratories are still critical but they are no longer the center of the research universe. They are important because they provide one or more key services – the ability to ask the right questions, the ability to understand the relevance of data or the ability to create unique research services not yet commercialized – but they are now only one link in a chain of service providers required to make a breakthrough research discovery. It is this shift in perspective that I believe will be difficult for some to make and why it won’t be easy for the next few years to get the heads of research laboratories to post their “services” online in the same way that core facilities and CROs are generally eager to do. It will happen, but old habits die hard.
mattoddchem 8:31 pm on October 8, 2012 Permalink |
Agreed – I think it’s very interesting the way things are changing. Thus in many academic drug discovery projects, the synthetic chemistry is being done by PhD students because that’s the way it’s always been done. An argument is made that it’s good “training” but I worry about that. After one has made one small molecule by doing an amide coupling, there is questionable added value in making 10 more. The point ought to be that we are training our students to think about new ways of doing things, and that might mean involving specialist research services along the chain of experiments.
Bill Hooker 11:04 am on October 6, 2012 Permalink |
Finally got around to working on the letter:
https://docs.google.com/document/d/1yUm1UdKuRczoj8f-DjEQbQnyuNPIbxK7GQUuD2FpNnk/edit
I made a new copy because I didn’t add anything substantive but I shortened and rearranged, which got ugly fast when I was trying to just leave comments. My experience has been that shorter and punchier is better, when reaching out to industry/business partners.
Hope that helps some.
mattoddchem 8:32 pm on October 8, 2012 Permalink |
Sincere thanks Bill – excellent. Will finalise and start sending out as soon as I overcome a minor inbox bubble.
Kevin Lustig 8:56 am on October 7, 2012 Permalink |
We’ve recently been trying a variant of your idea together with Jimmy Lin and his colleagues at the Rare Genomics Institute. We set up a Rare Disease Science Challenge for kids with rare diseases. We then reached out to the over 1100 vendors in Assay Depot’s network and asked for in kind donations of research services for the Challenge, including assays, models, consulting time, informatics tools etc. To date we have received commitment for more than $375,000 in services (and 10K cash) from a total of about 25 research vendors. After the launch of the Challenge on October 15th, the Rare Genomic Institute will team up families with research experts, who will use the donated services to craft an individualized drug discovery plan for each sick child. A team of well-known experts including Atul Butte from Stanford and Bernard Munos from Innothink will help judge the proposals. Facebook voting will determine the final winner (or two). Here is a link to a recent blog post if you are interested in getting more information: http://blog.assaydepot.com/rare-disease-science-challenge-call-to-action
We spent about 2 months soliciting donations and, although 385K is not insubstantial, I was a bit disappointed in the vendor response (25/1100 = 2.3% response rate). The success we did have was clearly due to the fact that we had a very compelling story. Most rare disease patients are kids that die before age 10, and despite the name “Rare Diseases” affect 1 in 10 Americans so many people are directly or indirectly affected by a rare disease. I also believe that the vendors got involved because they felt that it would be good marketing exposure they could receive without a cash payment.
If you are interested, we’d be happy to help get the word out about your open science work directly to our network through our monthly vendor newsletter.
mattoddchem 8:28 pm on October 8, 2012 Permalink |
That’s very interesting, Kevin. Yes, this is similar to the idea I outlined. Your success rate gives an interesting guide to how many CROs we might have to contact here. In answer to your kind offer, then yes we’d clearly love to be brought to the attention of your network. We’ve actually submitted a request for synthesis of a few compounds in the usual way. The relevant structures are here:
http://www.thesynapticleap.org/node/416
…but if you could flag up the need for a few mgs of the specified structures, with perhaps a link to this blog post, that would be enormously helpful, thank you.
mattoddchem 10:01 pm on October 8, 2012 Permalink |
Some more background on PILCH, and how it coordinates the supply and demand of pro bono activities.
http://www.liv.asn.au/News-and-Publications/Law-Institute-Journal/Archived-Issues/LIJ-October-2012/In-the-public-interest
Open Source Malaria’s First Paper | Intermolecular 10:16 pm on September 14, 2016 Permalink |
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