Gaps in in vivo research and their long term effect on TB

So my last posting here described a small slideset shared on figshare, the PDF is now on slideshare too .. I am increasingly drawn back to slide 21 which resulted from work to be submitted very soon in a different format by collaborators in the TB space (Joel Freundlich, Richard Pottorf, Robert Reynolds, Antony Williams and Alex Clark)- more on this work later I hope. Well after curation of close to 800 cpds tested in an animal model one can graphically slice and dice the data. A rough ordering of the compounds by the approximate date of publication for different activities (active or not 1 or 0) for different molecule properties gives the plot in slide 21. Without giving too much of the paper away, this little plot actually says an awful lot. From the 194o’s to 1970 we found maybe 400 cpds with  in vivo data. From 2002 to now there are close to 300 compounds we found tested and in between there is a 30 year period were there are approximately 50 compounds with in vivo data in the animal model of interest. This got me thinking. I do not have the historical perspective of these years and TB research, so forgive me. I was born in 1970 after all, pretty much the break point. But it looks clear to me that everyone thought TB was done. Drug resistance and TB started roughly in the 1980s and still it took another 20 years for researchers to crank up the pipeline and get compounds tested in vivo. Wow, what were they thinking? I am not saying our data is definitive, we clearly do not have access to everything tested but just from the published literature we can see this pattern. Everyone talks about the valley of death in translation from the bench to the bedside. This is the first time I have seen data were we have a 30 year valley of death that was something that was clearly avoidable and created by mankinds shortsightedness. This cannot be attributed to technologies, changing approaches in drug discovery etc. I would have expected 300-400 compounds to be tested between 1970-2000 based on the historical rate of screening in vivo. Mankind fell short. Many more mice lived. And now I think we are paying the price for this trying to play catch up.

Leave a Reply

Your email address will not be published.

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>