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Sunday, August 07, 2011

Typing on Blue Paper

If you type 100 words a minute with ten years experience typing TPS forms on blue paper for ACME Products, what is your skill?

Typing

If you are the finance officer of a biotechnology company, what is your skill?

Finance

If you conduct research in a life science laboratory, what is your skill?

Research

The question however, is whether or not anyone conducts research in a biotechnology laboratory. Research is not about any particular piece of equipment or assay. An individual who can obtain a degree in science should have the ability to learn how to operate the various pieces of equipment. But biotechnology companies do not conduct research. The board will select the drug target and the antibody/siRNA or whatever is in fashion will be developed to address the target. Most often, they do not match target to technology and they one day will have to close up shop. What is missing is an understanding of research.

Research is an evolution. We begin with ignorance and evolve to understanding. Ignorance has an unpleasant connotation however, one that PhDs do not want associated with their work. Thus, they begin with an ignorance of their own ignorance. How many biotech PhDs have tried to make an antibody against amyloid beta? How many have used phage display to bind to amyloid beta? The concept is that they begin with the knowledge that something that binds to amyloid beta should prevent it from forming plaques in the brain and thus cure Alzheimer's patients. Research did not create that evolution of understanding. This stepwise cure for Alzheimer's has cost billions but has not panned out. There is something we don't know. We are still ignorant about the beginning of our research. Why are the plaques there?

As a result of the inability to admit our own ignorance, we have established a new paradigm for conducting research. We draw out mechanisms, such as we did with RNAi being used as a drug. The siRNA will enter the blood stream, go to its target and begin to reduce the translation of mRNA. Nothing else will happen and the target knock-out will cure or slow down the condition. Early on, it seemed that siRNA was knocking out targets. There was a leap of faith that this could be a drug. Since then we have a large body of evidence (both known and hidden from the light of day) that would lead us to think more about where this research emerged from. Did we begin from ignorance and evolve to understanding? It seems we began from a vague understanding and evolved to ignorance.

What does any of this have to do with identifying a persons skill? Does the secretary type 100 words per minute or does she specialize in typing on blue paper? A researcher in biotechnology is not a person who usually obtains 20 to 30 years of experience conducting research. Rather, they will begin their career as someone who is given the task of knocking out a target to effect a specific condition. The conditions are well documented so we assume the only way forward is to tackle the unknown of dealing with them. You will need molecular biology specialists, cell culture specialists, protein purification specialists, analytical machine operators, and so on. All of the people working in the laboratory are usually non-PhD research associates. Their careers begin with one of the above specialties and they advance their careers only in terms of years of experience. Typing is not enough. They must type on blue paper. For example, I've seen technicians with five years of experience running a Waters HPLC. The laboratory they apply to has Agilent HPLCs. They are out of the running. The skill is required by the researcher. It is not a skill that they must understand, thus they can make the mistake of not identifying what matters most. Do they want someone to effectively use the HPLC for its intended use or do they have an Agilent in their lab that no one knows how to turn on?

The researcher then, should be the person working to put all of the skilled technicians together to move from ignorance to understanding. The most in-demand researchers however are those who have the most patents and publications. The assumption here is that they have reached the level of understanding more often than those with less patents and publications. Science however is a superior way of thinking that takes great pains to distinguish between quantity and quality. Biotechnology is not science, it is a business. It needs experienced obedient workers to turn on the machines and do the paperwork. Research is handled by those who can most often get published and get patents. As a result the amount of useless patents and inaccurate publications have sky rocketed. The companies have had to return time and again to the point of ignorance, the point where research begins. It's not a bad place if you are a scientist. It is a place that fascinates and brings on the evolution of understanding. If you just spent $1.1 billion, such as Merck did on Sirna, it is a bad place to be. You just hired a bunch of people who all had experience typing on blue paper. Typing however, was not their specialty. Research was not their specialty. RNAi was.

Biotechnology has been reduced to mostly monoclonal antibody companies. They sometimes try to break up the molecule or make it more stable but these are bells and whistles that don't work very well. The business model remains, select target, make antibody, start clinical trials, partner or be acquired by big pharma. It's all just typing on blue paper specialists. Basic research, starting from a known ignorance, is the only way innovation will take place. Who has the courage to admit that they know how to type but they don't have any experience typing on blue paper?

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