Open Source Drug Discovery with the Malaria Box Compound Collection for Neglected Diseases and Beyond.

A major cause of the paucity of new starting points for drug discovery is the lack of interaction between academia and industry. Much of the global resource in biology is present in universities, whereas the focus of medicinal chemistry is still largely within industry. Open source drug discovery, with sharing of information, is clearly a first step towards overcoming this gap. But the interface could especially be bridged through a scale-up of open sharing of physical compounds, which would accelerate the finding of new starting points for drug discovery. The Medicines for Malaria Venture Malaria Box is a collection of over 400 compounds representing families of structures identified in phenotypic screens of pharmaceutical and academic libraries against the Plasmodium falciparum malaria parasite. The set has now been distributed to almost 200 research groups globally in the last two years, with the only stipulation that information from the screens is deposited in the public domain. This paper reports for the first time on 236 screens that have been carried out against the Malaria Box and compares these results with 55 assays that were previously published, in a format that allows a meta-analysis of the combined dataset. The combined biochemical and cellular assays presented here suggest mechanisms of action for 135 (34%) of the compounds active in killing multiple life-cycle stages of the malaria parasite, including asexual blood, liver, gametocyte, gametes and insect ookinete stages. In addition, many compounds demonstrated activity against other pathogens, showing hits in assays with 16 protozoa, 7 helminths, 9 bacterial and mycobacterial species, the dengue fever mosquito vector, and the NCI60 human cancer cell line panel of 60 human tumor cell lines. Toxicological, pharmacokinetic and metabolic properties were collected on all the compounds, assisting in the selection of the most promising candidates for murine proof-of-concept experiments and medicinal chemistry programs. The data for all of these assays are presented and analyzed to show how outstanding leads for many indications can be selected. These results reveal the immense potential for translating the dispersed expertise in biological assays involving human pathogens into drug discovery starting points, by providing open access to new families of molecules, and emphasize how a small additional investment made to help acquire and distribute compounds, and sharing the data, can catalyze drug discovery for dozens of different indications. Another lesson is that when multiple screens from different groups are run on the same library, results can be integrated quickly to select the most valuable starting points for subsequent medicinal chemistry efforts.

Implementing competency based admissions at the Albert Einstein College of Medicine.

The Albert Einstein College of Medicine (Einstein) was founded in 1955 during an era of limited access to medical school for women, racial minorities, and many religious and ethnic groups. Located in the Bronx, NY, Einstein seeks to educate physicians in an environment of state-of-the-art scientific inquiry while simultaneously fulfilling a deep commitment to serve its community by providing the highest quality clinical care. A founding principle of Einstein, the basis upon which Professor Einstein agreed to allow the use of his name, was that admission to the student body would be based entirely on merit. To accomplish this, Einstein has long used a 'holistic' approach to the evaluation of its applicants, actively seeking a diverse student body. More recently, in order to improve its ability to identify students with the potential to be outstanding physicians, who will both advance medical knowledge and serve the pressing health needs of a diverse community, the Committee on Admissions reexamined and restructured the requirements for admission. These have now been categorized as four 'Admissions Competencies' that an applicant must demonstrate. They include: 1) cocurricular activities and relevant experiences; 2) communication skills; 3) personal and professional development; and 4) knowledge. The purpose of this article is to describe the process that resulted in the introduction and implementation of this competency based approach to the admission process.