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Wednesday, September 14, 2011

Rice Fields

Once again Malcolm Gladwell has stopped me dead in my tracks and forced me to rush back to this ridiculous blog. The topic is rice fields. In Outliers Malcolm discusses Chinese peasants who meticulously set up their rice paddies. They have a clay bottom with mud and fertilizer base for the seeds. They are then flooded with water and tended to every day. There is a balance that is maintained by hand, not automation. What the peasants know is hard work and an exact science.

Conversely there are the peasants in Russia. They plant their seeds and hope for rain. Their form of farming relies on luck. The Russians believe that God will provide.

So what is the culture of biotechnology? On October 24, a meeting with the "leaders" in the field of sequencing genomes will convene. They believe that this is the future for medicine. Why? If you step back and take a different angle, you will see sequencing a genome as a research tool. One probability is that the future will be same as Retrogen or Qiagen. The people excited about it should have already done the kind of thinking that would make this tool desirable and not just another sequencing service for researchers. It is a tool. What to do with it?

Think of it this way. A prion is a mis-folded form of the PrP protein. The theory goes that the mis-folded protein causes the formation of plaques in the brain and eventually a horrific death. We now have a few end points to look for if we could just find a way of preventing the proteins from becoming mis-folded. We need a tool. That tool could be an antibody that only recognizes the mis-folded protein, not the normal PrP protein. The antibody will bind to the mis-folded protein and prevent its theoretical action of causing other PrP proteins to become mis-folded and joining hands to become a plaque. To be honest, I worked on such a project. Such an antibody is hard to find. We never found it nor has anyone else.

From the above paragraph the average sophmore should be able to create a list of projects one could embark on if they were magically handed the prion antibody. For example, coat 2 ELISA plates with 95 normal brain samples and 1 scrapie infected hamster. Test one plate with the anti-PrP antibody and the other with the new tool antibody. One plate will light up in all wells. The other plate will have only one well light up. Eureka! Next you move on to in vivo studies. You create analytical methods.

This type of research in fact takes place every day. We select targets, make antibodies and run them through our tests. Going back to the genome sequencing, we don't have a plan. Both situations are similar to the concept of planting seeds and hoping the Gods will provide. The board and the executives plant the seed and they leave the field work to the peasants. If the seed is strong and there is plenty of sunlight and rain, success will be certain.

Now back to the Chinese rice farmers. They do not take chances. They are extremely poor and failure is not an option. This is akin to what engineers do. If you make a car, everything must work. If the brakes go out or even if they squeak, you will have to go back to the drawing board. Therefore, each new version of car is built upon the history of making cars. Engineers develop the cars. Engineers develop the way in which a car is assembled. Engineers develop the assembly line!

Biotechnology executives however, have to hold public chat sessions where they discuss what can be done with the latest tool. They have given the problem some thought and are now ready to talk about it in public. In public speaking is what they are good at. Knowing what to do with new tools is not what they are good at. They are not like rice farmers or engineers. They are like Russian farmers who have planted a seed. A dust-bowl season will ruin the crop. That season is akin to a small handful of genetic researchers being the main customers of the $1000 human genome sequencing companies. The ideas that come from the stage of the upcoming meeting must inspire. They must convince the world that science is going to be turned upside down by this technology.

But we've heard this before. The human genome project created so many patents they had to end the practice of patenting genes. Where were the guys who knew what they were going to do with the genome sequence? Where are they now? The executives of the old companies got rich but what did we learn about our genome? Is it a useful tool? The new companies are like the old. They are hoping for someone, something to take a hold of their seeds and nurture them into a rich harvest for themselves. Whoever solves that problem won't be the ones up on the stage next October.

I've spoken about practical intelligence. A clever fellow with a high I.Q. can solve difficult math problems but he cannot necessarily become a successful human being. The rice farmers are peasants who live with little money. We on the other hand are successful humans with lots of money and comfortable lives. We rarely succeed. But facing the future of the human genome, who will solve the problem of "what to do with it?" It won't be the executives on the stage. It will be that guy with below average practical intelligence but above average problem solving skills. If biotechnology really wants to figure out what to do now, they have to put an end to the cheer leading, the mitigated speech and the low opinion of the peasants.

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