The first open source science project in which I was involved was one that derived an improved, realistic, inexpensive route to the active enantiomer of praziquantel. I've spoken about it many times over the years, and we published the science details and the open science mechanism. The project ran mainly 2009-2011, with most of the activity during a really fun sabbatical period I had in San Francisco Jan-June 2010. The point is that commercial racemic PZQ is super important as the medicine of choice for the neglected tropical disease schistosomiasis (Bilharzia), and also will be your cat/dog dewormer, but compliance is lessened because the medicine tastes terrible, and that taste arises mainly from the inactive enantiomer. So: make the active enantiomer, without the price going up, and we can improve the compliance while making the pill smaller.
The striking thing about the project was the speed and effectiveness of the open science. Highly qualified people contributed freely, mostly (about 75%) from the private sector, and accelerated the science to such an extent that we completed the project early. Many of the contributors were strangers to the core team, and I'm fairly sure that the contributions were made because the project was open. Again, the thing that is perhaps not understood (e.g., by folks who think that open science = just publishing open access) is that the contributions were made as the project was proceeding, and that those contributions changed the direction of the project. This is an essential feature of what I think of as open science. The possibility that others change what you're doing.
The other interesting feature was the way that our project was pitted against another that was working in secret within a contract research organisation. While I was initially miffed that we'd been secretly competing against another organisation (I think this was the devilish genius of our WHO collaborator, Piero Olliaro), the routes that emerged were not too dissimilar, and this acted as a kind of benchmarking exercise for an open team of mostly volunteers (30 or so people, in public) vs. a dedicated CRO (I think maybe 2 people full time, in secret). The CRO could see what we were doing, but we were unaware of the existence of the CRO - I think we were tipped off by a comment on Derek Lowe's blog.
Since then? Well, once we demonstrated that the asset, (R)-PZQ (it's being called arpraziquantel, doing away with the fiddly "(R)-"), could be made inexpensively and simply under ambient conditions on a gram scale, we were kind of done. The TDR division in WHO took what we'd achieved and we in the project kind of parted company with the downstream development, which is a logical thing to do. We were the science team, and we'd handed things off to those with expertise in public health and development.
The generics company Cipla were looking at scaling up what we'd found. I visited the site in Mumbai to speak to Yusuf Hamied about things and saw a truly beautiful kilo of enantiopure PZQ sitting there, and saw that one of the lead chemists was examining one of the TLCs from our open lab notebooks. Subsequently I was made aware of the Paediatric Praziquantel Consortium's work. It is they who are now really progressing things and doing wonderful work translating (R)-PZQ to widespread use. This has involved additional trials, e.g. to check that the single enantiomer is actually worth using - that the improvement in taste is worth it in terms of compliance.
And it was recently announced that Merck has signed a contract manufacturing agreement, which is wonderful news. I'm not sure of the route they're using (I've asked - a company in Nairobi is making it) but I like to think our public and heavily road-tested solution helped to move everything along in terms of feasibility, benchmarking etc.
Remember: this is an open asset - there is no IP protection, yet the molecule is progressing towards real use in the field and would positively impact public health for so many people. Throughout the project, which was a close alliance with WHO/TDR, we never had any doubt this would be a problem. There are other important examples of medicines that were brought through to patients unencumbered by protected IP/patents and which are helping people, like fexinidazole for sleeping sickness (in which Els Torreele played a major role) and ASAQ/Coarsucam for malaria. I so very much hope that (R)-PZQ joins them.
The first open source science project in which I was involved was one that derived an improved, realistic, inexpensive route to the active enantiomer of praziquantel. I've spoken about it many times over the years, and we published the science details and the open science mechanism. The project ran mainly 2009-2011, with most of the activity during a really fun sabbatical period I had in San Francisco Jan-June 2010. The point is that commercial racemic PZQ is super important as the medicine of choice for the neglected tropical disease schistosomiasis (Bilharzia), and also will be your cat/dog dewormer, but compliance is lessened because the medicine tastes terrible, and that taste arises mainly from the inactive enantiomer. So: make the active enantiomer, without the price going up, and we can improve the compliance while making the pill smaller.
The striking thing about the project was the speed and effectiveness of the open science. Highly qualified people contributed freely, mostly (about 75%) from the private sector, and accelerated the science to such an extent that we completed the project early. Many of the contributors were strangers to the core team, and I'm fairly sure that the contributions were made because the project was open. Again, the thing that is perhaps not understood (e.g., by folks who think that open science = just publishing open access) is that the contributions were made as the project was proceeding, and that those contributions changed the direction of the project. This is an essential feature of what I think of as open science. The possibility that others change what you're doing.
The other interesting feature was the way that our project was pitted against another that was working in secret within a contract research organisation. While I was initially miffed that we'd been secretly competing against another organisation (I think this was the devilish genius of our WHO collaborator, Piero Olliaro), the routes that emerged were not too dissimilar, and this acted as a kind of benchmarking exercise for an open team of mostly volunteers (30 or so people, in public) vs. a dedicated CRO (I think maybe 2 people full time, in secret). The CRO could see what we were doing, but we were unaware of the existence of the CRO - I think we were tipped off by a comment on Derek Lowe's blog.
Since then? Well, once we demonstrated that the asset, (R)-PZQ (it's being called arpraziquantel, doing away with the fiddly "(R)-"), could be made inexpensively and simply under ambient conditions on a gram scale, we were kind of done. The TDR division in WHO took what we'd achieved and we in the project kind of parted company with the downstream development, which is a logical thing to do. We were the science team, and we'd handed things off to those with expertise in public health and development.
The generics company Cipla were looking at scaling up what we'd found. I visited the site in Mumbai to speak to Yusuf Hamied about things and saw a truly beautiful kilo of enantiopure PZQ sitting there, and saw that one of the lead chemists was examining one of the TLCs from our open lab notebooks. Subsequently I was made aware of the Paediatric Praziquantel Consortium's work. It is they who are now really progressing things and doing wonderful work translating (R)-PZQ to widespread use. This has involved additional trials, e.g. to check that the single enantiomer is actually worth using - that the improvement in taste is worth it in terms of compliance.
And it was recently announced that Merck has signed a contract manufacturing agreement, which is wonderful news. I'm not sure of the route they're using (I've asked - a company in Nairobi is making it) but I like to think our public and heavily road-tested solution helped to move everything along in terms of feasibility, benchmarking etc.
Remember: this is an open asset - there is no IP protection, yet the molecule is progressing towards real use in the field and would positively impact public health for so many people. Throughout the project, which was a close alliance with WHO/TDR, we never had any doubt this would be a problem. There are other important examples of medicines that were brought through to patients unencumbered by protected IP/patents and which are helping people, like fexinidazole for sleeping sickness (in which Els Torreele played a major role) and ASAQ/Coarsucam for malaria. I so very much hope that (R)-PZQ joins them.
Open science can deliver medicines.