Curiosity, Science, HTS and is newer really better?

I have been a humble participant in several discussions in the last few weeks that have been stimulated by the paper on dispensing and IC50 differences between pipette tips and acoustic handling. I am still parsing them, but what really stands out is the complete lack of exhaustive comparisons in academic screening centers between different dispensing methods. I have been thinking a little bit more about this.

What happened to curiosity and science? Did anyone ever ask the question – what is the best way to dispense liquids for high throughput screens (be it tips, pins, acoustic, etc)? Did anyone ever do a well controlled comparison? Well it appears not.

Apparently it seems that each academic HTS screening center (and some are listed here) has done it’s own thing in this regard (what happened to best practices?). And that usually means just going with A. the technology they know best, B. the technology they could afford or C. they went for the technology they thought was ‘the best’. This is comparable to A. walking, B.  cycling, or C. buying a Ferrari when a Ford would work just as well.

So in the rush for academic funding no one ever thought to go after a grant to define the best methods to actually do HTS? I honestly would have expected academia to lead the way here because isn’t academia full of scientists and don’t they have the curiosity to wonder is the current way of doing something optimal? Screening more compounds and getting more hits (or getting more funding) seem to have been the things motivating scientists, and not curiosity. Don’t get me wrong, I am not assuming newer is really better but at least do the head to head comparisons. Determine the strengths and weaknesses of different methods, identify the physicochemical properties of compounds that may present issues with each method and then tell the world. Pharma has done some of these comparisons and they have shared some of the data – but its akin to letting the world take a quick peek at their insights rather than being able to dig into it deeply.

So what do I propose? The NIH, or some other big organization should fund: 1. a workshop on ‘issues with dispensing’ bringing academics and pharma together 2. the head to head comparison described above with a diverse library of compounds and across many different types and complexities of assays (and publish it in an open journal) 3. come up with recommendations for HTS centers, dispensing hardware manufactures, compound library vendors, databases, software developers, medicinal chemists, computational chemists etc.

Yes we are drowning in biological data, I am just not convinced its as good as it could be. I am also curious to see if we could get better data and more hits in our HTS if we used different methods for dispensing. I will be keen to see if others want to do what should have been done long ago. The experiment.




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