By Declan Butler

A chemist--and social entrepreneur--in Australia is launching an open-source research project to develop a more potent form of a front-line drug against the debilitating neglected tropical disease schistosomiasis.

Matthew Todd of the University of Sydney hopes to persuade research chemists across the world to share laboratory time and expertise in a collaborative effort to find a cheap and efficient synthesis of the drug praziquantel. All results will be published in almost real time on the project's Web site--free of intellectual property restrictions--and later in journals, with substantial contributors becoming authors on any resulting papers.

Todd, who is currently on a six-month sabbatical at Stanford University in California, had been playing with the idea since 2006. He hired a post-doc last month after receiving three-year funding of Aus$400,000 for the project--mostly from the Australian government with Aus$75,000 coming from the World Health Organization--to start putting it into practice.

"My funded project is intended to be the kernel, to which anyone can add," Todd says. He hopes that the project will become a successful example of open-source science, and open-source 'wet lab' chemistry in particular, a concept that has been slow to take off.

A big ask

Schistosomiasis, which is caused by flatworms transmitted by freshwater snails, affects some 200 million people in Africa, Asia and Latin America. Some neglected diseases have recently benefited from drug companies' donations of billions of tablets, or from donors negotiating bulk distribution deals at cheap rates. But schistosomiasis hasn't enjoyed such generosity. Supply of the treatment praziquantel is, according to World Health Organization estimates, around 10 percent of demand.

"Availability of praziquantel is the big stumbling block for us," says Alan Fenwick, a parasitologist at Imperial College London who heads the global Schistosomiasis Control Initiative. Last year, public-health programs could only obtain 50 million of the 171 million tablets hoped for.

Todd accepts that praziquantel supply is the main bottleneck in treating schistosomiasis. But he also hopes to improve the synthesis of the drug. Praziquantel is manufactured as a mixture of two mirror-image molecular structures, or enantiomers, only one of which is active against the disease. If there was a cheap way to synthesize only the active enantiomer, this would make it more potent gram for gram. Fenwick feels the project is unlikely to be a major panacea, but sees it as "a very interesting academic exercise." An improved synthesis, however, could lead to more efficient ways of producing the chemical, as well as a purer end product.

Todd developed a synthetic route to several compounds while a postdoc in the United States that he realized might also provide a way to make praziquantel. The chemistry suggests several possible routes to enantioselective synthesis, with the difficulty being finding one that is efficient and amenable to manufacture the drug cheaply on the tonne scale.

Collaborate to innovate

The extent of the challenge hit Todd on his honeymoon, he recalls: "I realized there was no way we were going to solve the synthesis problem on our own." Only by organizing the research as a low-overhead open-science project, he thought, could it garner the critical mass of collective wisdom, manpower and lab space needed.

"It will be interesting to see if enough of Todd's colleagues will embrace this approach to enable the open-source approach to take root and grow," says Wayne Best, managing director of Epichem, a company based at Murdoch University in Perth that supplies medicinal chemistry products to the drug industry. Best himself has chipped in with suggestions for alternative synthesis routes at the project's online home within 'the Synaptic Leap', an open-science website for sharing data on neglected diseases.

Transposing the open-source software model to chemistry and drug discovery generally poses challenges, says Best, in particular because in addition to sharing data, laboratory and production infrastructure is also needed. But he is upbeat about the praziquantel project. "It is focused on solving a very specific chemistry problem which does not require the complex multidisciplinary collaboration and infrastructure of a full-blown drug-discovery project, and it has a good chance of success," he says.