Protocols in drug discovery

This special issue of SLAS Discovery is unique. Rather than focusing on an assay technology, disease area, or molecular target, it instead serves to introduce a new article type- Protocols- that will join Reviews, Commentaries, Research Articles and Technical Notes on an ongoing basis in future issues.

Communicating scientific methods has been as important for the development of the modern scientific enterprise as communication of scientific results. Reviewing the history of scientific communications, Hull described how in pre-scientific times findings would be published in the form of coded “anagrams” []. These served to establish priority while obscuring key details, giving inventors sole use of their advances while their competitors labored to decipher the code. As scientific societies and their publications proliferated in later centuries, sharing as much information as possible, including details of methods and procedures that would once have been kept closely guarded secrets, helped foster technological advances that have lifted billions out of poverty and eliminated or cured many once-deadly diseases.

In papers up through the 1940’s, methods are found interspersed throughout the text. The IMRAD format (reviewed Sollaci et al, 2004 []), which came into increasingly widespread use in the 1950’s and is now in one form or another essentially universal, segregated methods into their own section, providing readers with a single place where they could expect to find experimental details. Today, whether placed before the results or at a paper's end, it is expected that experimental reagents, equipment, and procedures will be described in a methods section. However, as anyone who has had the experience of relying on a paper to implement a new procedure in the lab knows, it is rare to find sufficient detail in most materials and methods sections to make the process painless. This is, one hopes, not a latent vestige of the tendency to secrecy from science's prehistory but rather the unfortunate consequence of limitations of space and word counts.

Articles devoted specifically to detailed descriptions of methods proved to be extremely important during the period in which IMRAD was being adopted. Lowry's method for quantifying protein [], for example, has been referenced more than 300,000 times, making it the most highly cited paper in all of biology. Papers devoted to methods circumvent the space limits that constrain most method sections, but a big step in the way research methods are communicated came in the 1980’s. First Methods in Molecular Biology (1983) and then Current Protocols in Molecular Biology (1987) began to publish detailed protocols intended to provide researchers with far more detail about the materials, methods and procedures needed to conduct a particular experiment than was possible in a typical research article. Protocols are far more than just expanded methods sections. They typically include sourcing information about critical reagents and suggest potential alternatives, provide recipes for solutions, detail all the steps involved in a procedure and how long each takes, outline potential break points, present detailed troubleshooting information, and give users criteria they can use to gauge whether the protocol is functioning correctly in their own hands. The appetite for this kind of publication is supported by how robustly the format has flourished. More than 2000 volumes of Methods in Molecular Biology have been published, and by 2018, there were 18 distinct Current Protocols subject areas being offered (although these have now been collapsed into one online publication). New publications devoted to protocols have continued to appear in the years since.

Since there are already so many outlets for protocols, why did we launch the article type at SLAS Discovery? The SLAS community has unique interests, and we feel that SLAS Discovery is the best place to present the protocols that meet them. The six contributions in this issue cover a wide range of topics of interest to the readers of SLAS and serve as an excellent introduction to our implementation of the format. Carragher and colleagues from the University of Edinburgh contribute a protocol for using a cellular ubiquitination reporter in high-content imaging analysis of patient-derived cancer cells grown in 3-D culture []. Dickson et al. from AstraZeneca describe how to implement high-throughput CRISPR-mediated gene silencing in primary lung epithelial cells and offer suggestions as to how the method could be adapted to other primary cell types []. Feodoroff et al. from the University of Helsinki provide step-by-step instructions for conducting 3-D drug-sensitivity and resistance measurements in patient-derived cancer cells using readouts based on either luminescence or imaging []. In another contribution from AstraZeneca, Mullooly and coauthors describe how to isolate primary pancreatic islets and conduct high-content imaging assays with them []. Papandreou et al. of University College London's Institute of Child Health detail the steps involved in differentiating IPSCs into dopaminergic progenitor cells and conducting an LC-3 based assay using high-content imaging []. Finally, Spicer and colleagues from University of Florida's Scripps Biomedical Research provide a protocol for testing natural products in NSCLC cell lines grown as spheroids []. We have no doubt that each of these contributions will be of great interest to our readers.

Because protocols are so different in scope than regular research articles, the Guest Editors of this special issue worked together to craft a specific set of Instructions for Authors for protocols, and then worked with the authors who contributed submissions for the special issue and served as our test subjects to make sure those instructions could actually be translated into appropriate submissions. We are grateful to them for participating in the experiment. To ensure that the format really suits the SLAS community, we invite your feedback about this special issue and about future Protocols as they appear. We already discussed the importance of communication. Let us know what works, and what does not. Tell us if we need to modify our instructions to authors or alter the scope of articles we publish. If you have protocols that you use in your lab that you think will be of interest, we would love to consider them. If you can think of protocols that you would like to see in SLAS Discovery, let us know and we will try to find the best group to provide them. It is our sincere hope that this special issue will mark the beginning of something valuable.