"Unknown Unknowns" in Synthetic Biology

Update: Ash (@curiouswavefn) found a similarly structured article, this one in J. Med. Chem.

Somehow, I don't recall seeing this gem anywhere on the chemblogosphere...

Famed natural products chemist Jon Clardy wrote a 2014 perspective article in ACS Synthetic Biology. Interestingly he structured the content after former U.S. Secretary of Defense* Donald H. Rumsfeld's 2002 "There are known knowns" testimony. Remember it?

"...as we know, there are known knowns; there are things we know we know. We also know there are known unknowns; that is to say we know there are some things we do not know. But there are also unknown unknowns -- the ones we don't know we don't know."

Per the Clardy review, artemisinin (antimalarial) represents one of synthetic biology's well-researched "known knowns." Moving synthetic gene clusters for cryptic metabolites into more easily-cultivated host organisms meets the "known unknowns" criteria, whilst uncovering novel natural products with novel gene clusters and unidentified biological roles captures syn-bio's "unknown unknowns."

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*And, lest we forget, former CEO of Searle Pharmaceuticals - poetically apt, here?