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Tuesday, December 13, 2011

RNAi Strikes Again

It appears that the only thing RNA interference has accomplished thus far is a whole lot of disappointment. After my first RNAi experiment worked I was on board. We knocked out IL2 which led to an inhibition of osteoclast formation. Of course that was early on in the research. I later came to the conclusion that the inhibition of osteoclast formation was a fluke. Did I forget to add RANK-L? Would another day of observation have resulted in a full bloom of osteoclasts? As is normal in unreported science, the result was unclear. The probability of what we were hoping for (RNA interference) seemed to diminish with each new attempt at repeating the IL2 knockout.

The company I was working for soon ran out of cash and shut down having never repeated that experiment. Many laboratory workers tried but none could reproduce the results of that simple experiment. The way this type of science works is to have a desired result or even better, a one time observation, and force it to be the truth. The Beer and Pizza diet began. What concentration of RANK-L was used? Where did you buy the cells? Different technicians were brought in to overcome the incompetence of the last. All the while our successful experiment was presented to the investment world in 3 perfectly understandable slides. Just add RNA and away goes osteoclastogenesis.

The reason we went after IL2 was because we were a Bioinformatics company. We alone made the connection of IL2 to the RANK pathway using Bioinformatics. For that brief moment of success, we had added laboratory evidence. It brought out the worst in everyone. We needed this to be true. Our company was hurting and eventually filed for Chapter 7 bankruptcy. If IL 2 had become a drug target for Osteoporosis it would have changed everything.

RNA interference and IL 2 research continue however, with expected outcomes. AVI Biopharma (self proclaimed global leader in RNA based therapeutics) is axing 28% of its staff after missing out on a potentially huge federal contract to make an RNA-based treatment against pandemic flu. RNAi is also used by Dr. Steven Elledge.
Using the power of small interfering RNAs (siRNAs) to silence gene expression, we are now undertaking loss-of-function screens in mammalian cells.
Why is such a powerful research tool involved in such a curious story as the one coming from Dr. Elledge's laboratory?

IL 2 is in the news lately with a new retraction from the Bulfone Paus saga.

RNAi and IL2 research could one day lead to important information that will advance the life sciences. What I do is merely research. We find pieces of evidence and we try to figure out what is really going on. The complexity of a pathway is not simply understood by knocking out one of the many proteins involved. Nor is the complexity of RNAi understood by witnessing the many cases of gel manipulation in major publications from Harvard professors. It is odd but not direct evidence that RNAi does not work. IL2 is involved in a few sketchy cases of misconduct as well. It proves nothing.

All we have here is job loss and possible scientific misconduct associated with a couple areas of popular research being conducted by highly successful scientists. Are they Cargo Cult leaders? No comment. Is science correcting itself? Yes.


Anonymous said...

You should work with Jörg Zwirner:

Some SJ Elledge updates:-



Anonymous said...

New Bulfone-Paus retraction (running total 13 retractions) without the Russian postdocs who were blamed for the earlier retraction of 12 papers in sight.