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Subject:  Re: NuSi (...and Taubes) Date:  10/4/2012  5:53 AM
Author:  OleDocJ Number:  37935 of 45866

I think it's OleDoc that once said you have to be prepared to be "wrong" in science and that's true.

Well, I don't recall having said that, but it is true. I can't begin to estimate the number of my "great ideas" that turned out to be flat out wrong! That is the way creative science works. Most hypotheses get shot down soon after the data starts to come in.

As for serendipity, I recall a quote by someone (don't remember who) who said "Serendipity favors the prepared mind."

One of my most signigicant contributions to scientific knowledge was the discovery of oligosaccharide trimming in glycoprotein biosynthesis. While I was a grad student, my advisor asked me if the oligosaccharides could possibly be transferred "en bloc" to proteins in a fashion similar to the biosynthesis of bacterial cell wall glycoproteins. I adamantly insisted no, they were totally different. And they are.

However, 3 years later, I discovered that they were, indeed, transferred "en bloc" to proteins by novel dolichyl-pyrophosphatidyl-oligosaccharide donors. However, they were transferred as oligomannosyl structures which had to be "trimmed" back to a trimannosyl core before being elongated into the final structure. I coined the word "trimming" to describe this process. It was a novel concept in macromolecular biosynthesis at that time. The first example of biosynthesis by creating a macromolecule, trimming it back, and then re-elongating it with different components.

I should have gotten a Nobel prize, but I didn't!!!

That was serendipity favoring the prepared mind. One key ingredient in the discovery was having isolated an enzyme from bacteria that could cleave the oligomannosyl structures but not the "trimmed" structures. And I also had purified enzymes which could cleave the "trimmed" structures, but not the oligomannosyl structures.

All of the pieces fell into place, serendipitously. But, even after we did the critical experiment, it took us a couple of days to come up with the "Holy S#!t!!!" conclusion. It was a totally novel concept at the time.

I'm still waiting for Stockholm to come to their senses and give me my Nobel Prize!!!

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