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Monday, August 29, 2011

What To Do With It

It was not a beautiful paper.

Next came the patents. The news that came out today is that the U.S. Patent and Trademark Office (USPTO) has issued a Notice of Allowance for our patent application.

A primary advantage of this patented peptide library is the ability to rapidly screen and identify novel peptides that exhibit cell specific targeting characteristics for directed delivery of nucleic acid therapeutics," said the Chief Scientific Officer. "Delivery remains a significant challenge in the nucleic acid therapeutic space, and peptides with high affinity and specificity are expected to be a fundamental component to developing delivery approaches to a wide spectrum of tissues and cell types. In addition, the library may also be exploited to screen for peptides that function as specific antagonists, agonists or generally exhibit drug like properties.

The only problem is that the library has no ability to do the things described above. It was a dud. The obedient workers did everything they could but they couldn't get the results that validate the statements of the Chief Scientific Officer quoted here.

The CSO didn't mention that the team who developed and tested the library were sacked. They needed to go out and find someone who could figure out what to do with that library.

There are very few people with the expertise and resources to perform this kind of science.

"What to do with it?" was always the question. There was no conversation about "what to do with it" other than use it to target this cell or that cell. But how? That was the scientific "wealth into the system" that Feynman speaks of. Everything else was what Kurt Vonnegut referred to as "Kit Science" in Cat's Cradle. We had molecular biology kits, phage display kits, and we did some cell culture work. We got our patents and paper. But what should we have done with the library?

A lot of scientists I've worked with believe that there is some clever thing we didn't think of. When we got the orders to test the library against specific cells there was no discussion about the possibility that it wouldn't work. We tested the random thoughts of the leaders, various methods of treating the cells, different buffers and so on. When about 100 random thoughts had been tested they told us to go home. It was a relief.

But it doesn't work. No airplanes land. So
I call these things cargo cult science, because they follow all the
apparent precepts and forms of scientific investigation, but
they're missing something essential, because the planes don't land.

Now it behooves me, of course, to tell you what they're missing.
But it would be just about as difficult to explain to the South Sea
Islanders how they have to arrange things so that they get some
wealth in their system. It is not something simple like telling
them how to improve the shapes of the earphones. But there is one
feature I notice that is generally missing in cargo cult science.
That is the idea that we all hope you have learned in studying
science in school--we never explicitly say what this is, but just
hope that you catch on by all the examples of scientific

The CSO makes the claim that "peptides with high affinity and specificity are expected to be a fundamental component to developing delivery approaches to a wide spectrum of tissues and cell types". Why are they expected to contribute to this Holy Grail of RNAi technology? How will it work? Feynman also said:

You can know the name of a bird in all the languages of the world, but when you're finished, you'll know absolutely nothing whatever about the bird... So let's look at the bird and see what it's doing -- that's what counts.

I think of the peptide in this library as the name of a bird. They are looking for that name spelled out in amino acid letters. But even if they find it they will still know nothing about the peptide. They have to see what it's doing. How will they do that? Once again, "what to do with it?". Who will ask the question?

There is nothing wrong with not knowing something. That is why we do research. The problem comes when we want to believe something so much that we accept false answers. This library is just a library. It was not conceived of by someone who had any idea what to do with it. That person, and all of the others are gone now. The CSO quoted above inherited the library and he doesn't know what to do with it. Somehow he's figured out that it will be fundamental to solving the RNAi delivery problem. How will he know when they've found the magic RNAi delivery peptide? I guess they'll know it when they see it.

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