Douglas Connect is one of the winners of the latest CRACK IT Challenge, an industry-sponsored competition promoting the development of solutions based on the 3Rs principles of refining, reducing and replacing animal testing.

Part scientific research consultant, part data scientist and software developer, Douglas Connect is an unusual hybrid bringing specialized scientific and technical solutions to a number of different fields.

Douglas Connect’s winning proposal will address evaluation of Developmental and Reproductive Toxicological (DART) issues based on assessments against biological pathways. The Swiss company, now operating in the US from North Carolina’s Research Triangle Park, is building knowledge infrastructure to support the use of new methods for screening in decision making. This platform will support the scientific and industrial toxicology community working together.

What effect does a particular chemical have on fertility, the unborn child or childhood development? To find out, scientists carry out Developmental and Reproductive Toxicity (DART) studies. But standard animal-based DART assessments have a number of drawbacks. They require large numbers of animals (up to 800 rats and 900 rabbits for a single study), the process is expensive, and it takes a lot of time to complete the study compared to the time desired for decision making, e.g., in product development. Finally, the applicability of the results of an animal study to human health may not always be certain.

So, there is a lot of interest in reducing animal testing by using new alternatives, such as tests on non-mammalian, but orthologous, species (e.g., zebrafish, nematodes and Dictyostelium slime molds), combined with computer models.

NC3Rs and alternatives to animal testing

The British National Center for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) is one of the leading organizations in Europe supporting the use and development of alternative methodologies. It works with scientists and organizations (universities, industry, other research funders, regulatory authorities) across the life science sector, nationally and internationally, towards the development and implementation of new strategies to put the 3Rs into practice.

One of the most visible activities of NC3Rs is the annual CRACK IT Challenge, an open innovation program supported by industrial partners. CRACK IT’s goal is to develop marketable products and improve business processes to reduce the use of animals in research.

“The CRACK IT Challenge provides an industry sponsor-driven framework to bring teams together to work on solving problems and developing new products and better business processes with 3Rs impact. Such open innovation initiatives promise advances, but lack of access to data can impede progress,” says Dr. Barry Hardy, CEO, Douglas Connect.

This year’s CRACK IT set three challenges. One of them, DART Paths (‘Mapping developmental and reproductive toxicity genes and pathways for cross-species comparison of toxic compound effects’), aims to solve the problems inherent in DART assessment mentioned above. This year’s DART Paths competition was sponsored by Shell and Syngenta.

Two-phase competition to improve DART testing

For Phase 1, CRACK IT has awarded in total £300k for proof-of-concept research to three winning teams: SimOmics; the University of Applied Sciences, Utrecht; and Douglas Connect. The winner of Phase 1 will receive funding to develop its full project with input from the other two Phase 1 winners.

The three teams will take different approaches to develop a data model that maps orthologous DART genes and pathways for cross-species comparison, integrating available information on the relationship between specific genes and physiology, or specific compounds and effects, to better predict potential DART effects. The winner of the Phase 1 challenge will go on to develop a full version later this year in Phase 2.

Although the three teams will take different approaches, they could potentially be combined at some later date. “My sense is that we are working more in collaboration than in competition,” says Dr. Thomas Exner, Chief Scientific Officer, of Douglas Connect, based in Basel, Switzerland. “Our platform will allow the entire DART community to work together,” Dr. Exner explains.

Winning proposal

Douglas Connect and the Swiss Federal Institute of Aquatic Science and Technology (Eawag) collaborated on the winning proposal to develop infrastructure to model data related to DART. “Douglas Connect efforts will be on the knowledge infrastructure development, data integration and modelling, whereas Eawag will bring the required input on biological networks,” explains Douglas Connect’s Senior Toxicologist Dr. Tatyana Doktorova. “In the future, the scientific community will have all available  data on a flexible platform and can, in turn, generate and share new data.” “The networks will provide high confidence in DART predictions,” adds Dr. Anze Zupanic, head of Eawag’s Systems Biology Group. “We want to get rid of the noise and focus on the biologically important key events leading to DART.”

Douglas Connect = collaboration + community

Collaboration is not new to Douglas Connect. Active in building global scientific communities (OpenTox, OpenRiskNet, NanoCommons, etc.), Douglas Connect’s approach is to pull all concerned together, sharing data and experiences. “Our winning CRACK IT is a sign that sharing data as a community is no longer just academic thinking,” says Dr. Exner. “Major companies also see it as a winning system and are looking at experimental design to do it in the best way. But the software foundation must be professional so that data and knowledge is secured and preserved. Professional software solutions allow multiple users to have a reliable, community-driven way to share data.”

Similarly, the platform that Douglas Connect is building for CRACK IT will be open to the entire toxicology community. “We are creating a review of all the literature available that could be useful for making predictions in a scientifically condensed form,” says Dr. Exner. “For future researchers, our platform will provide access to the information in a structured way, as well as open up the possibility for computers to use it. We don’t mean to replace scientific journals – you can always go back to the original literature - but to condense the most important facts so that they can be used to predict adversity efficiently.”

“I am optimistic that our concept – community and data integration – will provide something special that the entire DART community can profit from,” he adds. “It has taken some change in thinking, but scientists and companies all seem to be coming around to our view that the open sharing of data and a community platform, is a valuable approach. Companies are understandably worried about sharing data, but they are now moving towards the idea that socializing their data can be beneficial. We bring the optimal organization to help them do that.”