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Sunday, May 27, 2012

Our Method

Descartes "Rules For The Direction of The Mind" can help the Cargo Cults understand "what is missing", why there is no "wealth in their system".

Rule 5 holds that complicated problems should be reduced to their simplest parts. We then apply our “intuition” to the simplest parts and work our way back to the larger problem. 

For our purposes here today, let's re-create a failed drug research project that most biotechnology companies in the past 30 years have attempted. The project is to make a drug against TNF apha.


The norm is that the executive staff and the board select a drug target based on profit potential and the probability of success. This involves faith in the sound decisions of the board of directors, advised by the scientific advisory board. The target is TNF alpha.  

Descartes: Rule 3 states that we should study objects that we ourselves can clearly deduce and refrain from conjecture and reliance on the work of others.

While others had proven TNF alpha to be a target that can bring the cargo, most TNF alpha projects failed. The notion that TNF alpha projects have a high probability of success is false. What the leaders tend to do, when selecting drug targets, is disguise conjecture as a scientific method.


Have the lab staff find a molecule that interacts with the target selected in step one. For our purposes we will generate an anti-TNF antibody.

Descartes: Rule 5 holds that complicated problems should be reduced to their simplest parts. We then apply our “intuition” to the simplest parts and work our way back to the larger problem.

The larger problem is getting the molecule to validate the conjecture and assumptions of management. The simple part is good biotechnology. We know how to make the antibody. Although this knowledge fades as we go higher into the ranks of leadership, it is a very solid foundation that gives the biotech credence. Where we begin to fall apart is when we move from the known technology into the unknown outcome of drug testing.


Descartes: Rule 2 holds that we should only study objects about which we can obtain “certain and evident cognition.” It is better not to study at all than to attempt a study when we can’t tell what’s right or wrong, true or false. 

In my experience scientists at higher levels do not participate at this level. Each company has different methods, for example, on testing the binding affinity of their antibody. Some use biacore. I've been told to do the same complicated calculations from ELISA assays. The higher ranking scientists need only have a vague idea as to how a drug is being tested at the early stages. Those who required me to obtain a binding constant from an ELISA assay, had a vague idea of how things work in the lab. In order to know whether or not the test will lead to "certain and evident cognition" much more attention would be required of the higher ranking scientists. This is a critical moment in the process that is soft. If the data comes back saying, for example, that the antibody had a weak binding affinity to TNF, the laboratory staff must explain why they think that to be the case. In other words, the lab staff must convince the scientists what the truth is. The scientists have positioned themselves only to judge the methods employed by the laboratory class rather than participate in establishing that an assay will provide certain and evident cognition. 

I've simplified the process down to its basic components. Where Descartes had rules for the direction of the mind, we have a very different set of rules. For each Descartes rule, we have a very specific unwritten rule of our own that does not match.

Rule 4 proposes that the mind requires a fixed method to discover truth. A method is defined as a set of reliable and simple rules. The goal of study through the method is to attain knowledge of all things. The human mind begins life in a pure state, and from the moment learning starts, the mind grows clouded. The method’s purpose is to return the mind to that pure state so that we can be certain of knowledge we attain.

As I've stated, there are no written methods for the larger problem. The simpler problems, (cloning, purifying, etc) have detailed written methods, SOPs. The laboratory staff must also write down specifics in a lab notebook, which often comes with a set of rules the lab staff must follow. Date each page, initial cross-outs... The scientists at the higher level have no method, no rules and no police other than themselves. Their commitment is to the illusion of success. Even if your biotech company fails, you now have experience running a biotech company. A publication is a publication, reproducible or not. Is this what Descartes outlined? 

We have a random method of discovery. It's a broken system. Reproducibility, to ensure that we are dealing with the truth, is not a part of our system. What would our rules be if we were forced to write them out in an attempt to explain how we spent so many billions on failed TNF projects? Failed Amyloid beta projects? Regardless of the target, the company, the technology, we would find a pattern. There is no set of reliable and simple rules. When you look into the laboratories, you will find that the minds have grown cloudy. If you look into the offices, you will find that the minds have grown corrupt. We need a method to return our collective mind to that pure state that led us to certainty in the past. 

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