A problem shared…

It isn’t just data sharing that is enjoying a boom period – reagent sharing could prove to be the next big thing to enable efficient and viable research.  

The availability of data is essential to scientific research, and is enabled by the commitment and good will of scientists. Life science research thrives on sharing reagents as well as information within the scientific community. This allows confidence in scientific findings to be built through reiterated independent validation of the data and expansion of existing knowledge. However, the difficulties of balancing cooperation and competitiveness and the limited resources to facilitate sharing have delayed the process considerably.

In a promising change of paradigm, platforms to allow sharing of reagents has become increasingly popular and new repositories are continuously being made available across the life science community. Here we give an overview of the benefits of sharing reagents and provide examples of established sharing platforms, with the hope that by being aware of the several available resources, scientists will be encouraged to take part in consolidating a community with the common goal of facilitating research. For an inventor, sharing means making the most of years spent researching and developing reagents which are not always necessarily included in a publication. In fact, what is revealed of one’s research in a scientific journal or at a conference can be the result of years of work, hordes of students, and possibly dozens of abandoned research tools. In addition to this, the development of research tools is a lengthy and expensive process. To maximise the benefits arising from these tools and to finance further investigations, inventors are quite understandably exploring new avenues to maximise the collaborative and commercial value of their research tools. The benefits to inventors for sharing reagents they have developed are manifold.

The benefits to inventors for sharing reagents they have developed are manifold.

Administration and distribution can be delegated to reagent repositories, where these processes are managed efficiently. Furthermore, reagent sharing platforms also offer a continuous flow of knowledge and material from inventors to end users; this enhances current scientific knowledge in two ways. The researcher in terms of accessibility and optimisation of experimental tools and to the inventor in the form of reputational credit and income. An added reassurance is that no research tool is lost or forgotten as researchers make their way through their scientific careers; no live material is altered by unnecessary proliferation, thereby preserving its original integrity and reliability; and reagents that have proven ineffective in a certain research area can be tested for their potential relevance in different research areas.

[caption id="attachment_52453" align="alignnone" width="540"] Reagent sharing allows for greater expansion of knowledge between researchers.[/caption]

Time-poor researchers can be helped immensely by the existence of these services which provide an overview of existing reagents and possibly serve as inspiration to drive their experiments. Reagents catalogued in such repositories often originate from peer-reviewed research, therefore the choice of tools available can be validated by other scientists furthering experimental reproducibility.  The existence of such repositories saves the researchers the trouble of dealing with every single request for their research tools, but it also paves the way for the commercialisation of these reagents, enabling their application within biomedical research while also promoting the exploration of their potential to aid pharmaceutical development.

Failing to collaborate and share information and reagents in many instances translated into poorer quality and success of the research

And if this wasn’t enough to highlight the benefits of sharing, in 2006 a study suggested a series of deterrents for not doing so. Failing to collaborate and share information and reagents in many instances translated into poorer quality and success of the research and, ultimately, in alienation from the scientific community and inferior academic knowledge and preparation¹.

Until recently, sharing of data and reagents most commonly occurred at conferences or often, through peer-to-peer communications. Reagents were frequently circulated following hard-to-find collaborations, based on material of unknown quality, and the legal and logistical obstacles encountered to circulate these tools were often enough of a deterrent to default to secrecy. Technology transfer offices (TTOs) were established to manage the intellectual property developed in many institutions. These entities, however, are often under-resourced to face the burden of entire research tool portfolios, and tend to prioritise research with therapeutic potential and spin outs. As such, TTO’s face similar resource difficulties in being able to engage with all scientists in their institutes due to the lack of capacity. Although TTOs represent a great means to introduce research tools to the outside world and to regulate their use, researching for materials in every existing TTO can often be a research project in itself. In order to regulate the transfer of such materials between organisations, material transfer agreements (MTAs) are available to define the legal rights and liabilities of the parties involved. MTAs however, despite their good intentions, are by necessity filled with complicated legal jargon, can be unreasonably restrictive and their negotiation and execution painfully slow.

In recent years, several research tool repositories have emerged to respond to these frustrations and to take on the responsibility of the administration that surrounds the regulated sharing of reagents. In 2004, for example, the plasmid repository Addgene was founded as a non-profit organisation that stores and promotes academically generated plasmids. Evidence of the value of that they provide to the community was so impactful that Addgene’s catalogue now holds over 45,000 plasmids sourced from more than 2,000 institutes worldwide.

[caption id="attachment_52413" align="alignnone" width="540"] Addgene holds a vast number of plasmids in its database.[/caption]

Addgene’s format is not completely new; reagent repositories in the United States have been around for almost 100 years. The American Type Culture Collection (ATCC) has been collecting, validating and distributing biological material such as cell lines, microorganisms and other material since 1925 and the first mouse model repository, the Jackson Laboratory, was set up in 1936. On the other side of the Atlantic, equivalent repositories include the European Collection of Authenticated Cell Cultures, established in 1985, and the MRC Harwell International Centre for Mouse Genetics, supported by Public Health England. With its facilities and resources, the MRC Harwell functions as the hub for all mouse studies in Europe and as an incredible archive of lines which are validated and distributed worldwide.

Martin Fray, Head of MRC-Harwell’s mouse archive says: “Generating and validating novel mouse strains is an expensive and time consuming undertaking. In order to maximise their scientific value these strains need to be protected from loss and shared across the community. Recognising of this imperative, the European Union and many National funding bodies created the EMMA consortium. EMMA now distributes over 500 gold standard mouse strains/year which confirms the value of the resource to current and future researchers.” When dealing with living organisms, especially with mouse models and cell lines, one of the benefits of gathering a large number of reagents into one repository is that they are constantly validated and subjected to quality control, thus increasing their value to researchers. This prevents the accumulation of pathogens that can alter the phenotype and minimises the genetic drift from the original founder of the population. It is in the very nature of living organisms to accumulate genetic variability and only a tightly regulated handling of these lines can ensure reliability of the model and reproducibility of the data².

 The validation of research tools through repositories comes not only from the repositories themselves.

As a next step towards sharing reagents, the EuroMabNet consortium has been initiated to standardise the generation and validation of tools, more specifically antibodies. It serves as a network of research laboratories across eleven European countries that are renowned for their competence in monoclonal antibody technology. These laboratories have partnered to generate a community of experts who aim at defining the best standardised practice and the most advanced methodologies for the development of properly characterised and reliable antibodies. Their contribution also extends to recommended methods in improving the way in which antibodies are selected and validated for experimental use, to address frustrations in research reproducibility. The validation of research tools through repositories comes not only from the repositories themselves. Potent tools are made globally available and serve to generate new independent publications, thereby substantiating the confidence and expertise around them while also increasing the profile of the inventor, who is credited through citation or acknowledgements. The reagents’ datasheets are constantly updated with new references, creating a real profile for each reagent.

A further step in this direction is offered at Ximbio, a business unit of Cancer Research Technology, the development and commercialisation arm of Cancer Research UK. In its approach, Ximbio is different from other repositories, which stem from high expertise around one specific tool type. Ximbio serves as an online platform where reagents of all types are sourced from inventors and TTOs, gathered, catalogued and made available to the community through an online platform. The website is user led; Ximbio relies on the feedback of the community by engaging researchers in supplementing reagent datasheets with references and technical data to increase the quality of research and facilitate the retrieval of reliable and specific tools, creating a real profile for each reagent. Because publishing is not a straightforward and rapid matter, any experience with research tools that precedes or is not included in a publication is also evaluated through personal reviews just as happens for any product offered on the market. Broad spectrum repositories, such as Ximbio in Europe and Kerafast in the US, represent a virtual space where researchers are introduced to the scientific community allowing their work to be recognised by external validation, but also the trusted place to search for scientific tools and possible collaborations.

The recent boom in data and sharing channels and the ever-evolving communication media have exposed the scientific community to endless possibilities and means of collaboration. This in turn has made it necessary to redefine the concept of sharing and to generate highways for a regulated flow of research which strikes a balance between the availability and authentication of scientific knowledge and just reward for researchers. Ultimately, there is a shift driving a scientific renaissance that can accelerate research progress immensely. The creation of online social communities, the increase in the number of open access journals, rise in sharing platforms for reagents and even data, for example Figshare, are all examples of this³.

[caption id="attachment_52454" align="alignnone" width="620"] The use of the cloud to share scientific information will enable greater collaborations worldwide.[/caption]

Actively promoting these channels amongst the scientific community by engaging with scientists will expand the scope for greater collaboration for the advancement of scientific research. Interacting in this way brings massive potential in accelerating the translation of data and of its progression into clinically useful therapies. It should be clear that by sharing, knowledge transferred from one researcher to another ultimately translates into higher research quality and the greater benefit for science and ultimately humanity.

Interacting in this way brings massive potential in accelerating the translation of data and of its progression into clinically useful therapies.

Encouragingly, these initiatives are proactively supported by granting agencies and scientific journals, who advocate cooperation amongst researchers. For example, the Nature Publishing Group has on several occasions’ publicised repositories such as the Chemical Probes Portal, which collates experts in the development of small molecules and serves as an online repository for validated material. Longer term, this enables researchers to share experiences and opinions in order to choose the best available tool for their research, thereby accelerating the introduction of these molecules into the clinic.

With the hardware for sharing all set and in place, and the support of powerful bodies in the life sciences, perhaps it is therefore a shift in the attitude of the scientific community that is now necessary for progress. After all, what is becoming apparent is that the seamless diffusion of research reagents enabled by repositories that foster the sharing and exchange of knowledge and materials can break down barriers in the work of scientists.

It is in the hands of the scientists.

Author

Cristina Pasi is a Portfolio Associate for Ximbio

References

1. Vogeli, C. et al. Acad. Med. 81, 128–136 (2006) 2. Lloyd, K. et al, Nature 522, 151–153 (2015) 3. Van Noorden, R. Nature, 512, 126-129 (2014)