Drug Baron

May 17, 2012
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Aiming for Average: Three traits where being best means being bang in the middle

Winning entrepreneurs tend not be average.  On traits as diverse as energy levels, intelligence and gut feeling the best entrepreneurs are usually off the graph.  Whether in sport, culture or business being average just doesn’t cut it.

Extremes often bring with them big benefits – but sometimes also big handicaps.  And working with some of the best, and most successful, brains in biotech over the last decade has highlighted to DrugBaron three particularly important character traits where extremes are definitely not associated with success.

So here, for the benefit of aspiring entrepreneurs in almost any field (and probably almost everyone else as well), are the traits where you should aspire to be average.

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April 19, 2012
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Is academic research finally coming of age?

DrugBaron has been concerned about the damage that failures in the system of publishing academic research is doing to the global pharmaceutical industry (and to much else besides) long before it became fashionable.  In the six months since  ’Rotten Foundations‘ was published here, we have seen an explosion in studies demonstrating the lack of reproducibility of almost everything emerging from the global academic endeavour.

Along with lack of reproducibility, the other big concern has been positive publication bias.  Exciting data supporting a proposition has, traditionally, been easier to publish in a good journal, and indeed many negative studies that call into question an established hypothesis fail to be published at all.

But a review of the table of contents for Nature on 19th April 2012 finally gives cause for tentative optimism. Nature is one of a handful of pre-eminent scientific journals, and few would doubt the prestige of articles published in its respected pages.  In just one issue (number 7394) there are three letters whose focus is entirely negative data, in three different scientific fields.

Treiber and colleagues show that the supposed ‘magneto-sensory’ neurons in the beak of birds thought to be responsible for their homing ability are in fact iron-rich macrophages.  The data blows a big hole in the well-accepted idea that we understand the molecular basis for magneto-location in birds.

Then the “IceCube Collaboration” pour  cold-water (appropriately enough) on the idea that “fireballs” of gamma-ray bursts are responsible for generating very energetic cosmic rays.

And Som and colleagues take a huge step towards dismantling the most widely held theory in earth sciences that high concentrations of greenhouse gases led to the warming of the early earth 2-3 billion years ago when the sun was 20% dimmer than it is now.  An elegant analysis of fossilised imprints of raindrops that fell 2.7 billion years ago lets them provide estimates of the density of the atmosphere at that time.

Exciting as each of these negative conclusions may be to those in their individual fields, the part that should grab the attention of every scientist was the coincidence of three negative findings gaining such prominence in the scientific literature.  For sure, even three swallows don’t make a summer, but perhaps the academic community itself as well as those guardians of the megaphone, the journal editors, are realising that the positive publication bias devalues the entire co-operative academic endeavour.

Lets hope this is the first step on the long road to seeing academic publishing re-establishing its status as the cutting-edge of human knowledge.

April 18, 2012
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Steps to rebuilding pharma R&D efficiency: “The Exupéry Principle” for medicinal chemistry

The efficiency of pharmaceutical R&D is declining.  That much is not in doubt: record R&D expenditure in the last decade has led to fewer drug approvals overall, and almost a complete drought in genuine, first-in-class innovation.  Set aside biologicals, and the performance in small molecules has been even more dire.  But that’s where the unanimity ends.  Dozens of hypotheses circulate to explain the decline in efficiency of small molecule drug development – and every part of the process has come under close scrutiny.

DrugBaron has extensively explored the weaknesses in preclinical and clinical development of the lead compound, but largely ignored the foundation of the whole process: designing the right molecule in the first place.  It turns out that tweaking medicinal chemistry strategies is just as urgent as tweaking development pathways.

“Applying the Exupéry Principle of design to consumer electronics has turned Apple into the world’s most valuable company.  Can it do the same for pharmaceuticals?”

The nub of the problem, it seems, is that pharma companies have overfished the pond.  Talking to visionary medicinal chemist Dr David Fox, I was shocked to discover that less than 1% of stable, easily-made small molecules have ever been synthesised, let alone tested for biological activity.  The other 99% represent virgin territory waiting for those clever enough to seek them out.  If there really are unexplored, unknown continents out there, how do we find them?  DrugBaron asked David Fox, and here is what he had to say…

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