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Tuesday, August 28, 2012

Barbeque Contests

While sitting around in the early morning I came across a Travel Network show on BBQ contests. The chefs are well known in BBQ circles. Many had won several competitions over and over. When the judges sit down to do their taste tests, they are blinded as to who prepared the food they are eating. Contrast that with the peer review system. Why do we bias our peers with our reputations? Don Polderman had over 500 publications. That is what the peer review system creates. The quantity of Dr. Ps work seemed to have some influence that the quality did not. The quality of work being done by the current group of human beings who are professional scientists in general, as judged by the lack of reproducibility of the work they publish, is not good. As judged by the peers it's the cream of the crop. Apologists and defenders would attack such a statement because science is... Fill in the the rest of that sentence yourself. Science is...

Science is blinding the judges at your BBQ contest to see if they can spot the best chef. Cargo Cult Science is authoritarian. The judges (peers) usually allow only one explanation. This prevents any further judging (unauthorized peer reviews) of the judges (the authoritarian peers). I would like to offer up an example of a Cargo Cult paper that I participated in, briefly why it's Cargo Cult and how the authoritarian system let this take place. It is in fact the norm in science and it is very hard for an Asberger Syndrome sufferer such as myself to understand.

You be the BBQ judge. I won't tell you my name or how I am associated with this paper. I will only offer up an alternative explanation to a few of the Cargo Cult points.

The paper is about the Trp cage and phage dispaly. The two real scientific discoveries were combined to create nonsense. Selecting what phage display library to use for your project is a random process. You select your library on conjecture and sometimes it works out for you. The excuse for its failure is usually that the library lacks the proper structure. Ironically, protein structures and folding are what make us who we are. Proteins are fascinating molecules that have so much complexity in what they can do its hard to imagine how the judges of this work did not question the oversimplification. Why did they think that the Trp cage would be in tact with the randomization of 7 of 20 amino acids? It is simply a sciencey narrative that was never scrutinized. Unlike the harder sciences that employ NMR and computer modeling to analyze the structure of this fascinating little protein, the life science biotechnology folk simply took the concept, drastically changed the amino acid sequence, and made the claim that it was still the Trp cage. Drawing the line from the Trp cage to a phage display scaffold and the finally to drug delivery molecules is a stretch of the imagination that boggles the mind. How did the judges not question the logic?

"Mutations were observed at a frequency dependent on display valency".  This is a classic Cargo Cult maneuver. A confusing sentence that looks sciencey but makes no sense. Cargo Cults like to emulate real airports. Cargo Cult Scientists do the same when the speak in hard to understand terms. In this case it's hard to understand that sentence because it is complete nonsense. The mutations were simply the result of having the DNA produced by human beings. Ten separate preparations of DNA were sent from Invitrogen. Only one or two was used to make the library. The rest of the preparations had too many "mutations". This is a detail that a judge/peer would not know to question. Anyone who has ever worked closely in molecular biology will have noticed that not all of their clones have the exact DNA sequences that they designed. You don't need them to because you have clones. You only need one good clone. Discard the rest. In phage display libraries however, you have to take the whole set. The authors came up with this explanation out of A) ignorance of bench level molecular biology and B) a need to be sciencey. The explanation is more sciencey than the more probable one, that is good as they could get it. Lacking the expertise of more skilled phage display teams, and lacking time, money and patience, led this group to banging out their first ever library and it was not perfect. But that lack of perfection was not "dependent of display valency".

The biggest Cargo Cultism about this paper is that somehow the combination of real science (the discovery of the Trp cage) and phage display technology will somehow lead to drug delivery technology. It's an idea. It's a thought. But that is all it is. Once tested it became clear that this was a half baked idea. It was dreamed up by higher ranking scientists who told lower ranking laboratory members to make it all come true. When you work in the industry of drug discovery however, you mustn't let people know that any of the ideas of the superiors are half baked. This paper is a prime example of how far people go to talk and talk and never let anyone look up into the sky to see if the airplanes are coming. Thought experiment: If a molecule binds to a target inside a human body, what will it do? In this case the molecules were suppose to be used as drug deliverers. Besides binding to a target, how would this work?

Those of us down below watching the wheels turn in the minds of our Cargo Cult leaders have little to say over the publications and the patents. We need them in fact to advance our careers. We put this stuff on our resumes and we tell everyone we're smart scientists. But I think I have Asbergers. I have a heightened sense of fairness and this paper is bullshit. Who can you tell? The judges are not blind. They do not like to entertain too many thoughts at once, especially if introduced by the wrong ilk.

Nothing came of the library. It was Cargo Cult. No one ever attempted to reproduce the salient points made in the paper. It was good for JBC because it appeared to be scientific. It was judged by peers impressed with the credentials of a couple of the authors. The journal had a new article that wouldn't cause any trouble. The authors have another publication to add to their total count. But it's bullshit. No one will ever use it again, like much of what gets published.

The paper itself is not important here at the CCS. It is what the paper represents. The authoritarian approach to right and wrong. The indifference of the leaders to what is right and wrong. It accomplished their goals but not the one that was suppose to have scientific merit, that the library had some special properties. The airplanes did not land. The company ultimately closed shop due to bigger Cargo Cult issues. One thing shut this company down however and it was the same thing that got this paper published. Bullshit. There are not blinded judges to weed out bullshit in the Cargo Cults. What the leaders say goes. Luckily for the fans of good BBQ, there is a way of judging right and wrong, good and bad. Someday science will catch up.

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