Doubly Distinguished
"Midrash" by George Barany (December 2013)

As soon as I received an e-mail from my long-time friend Jed Fisher with the news that one of my all-time scientific heroes, Frederick Sanger, had passed away, I knew that we had to memorialize this transition with a crossword puzzle. It was not difficult to recruit Marjorie Russel and Michael Hanko to join this effort, and we later benefited from the insightful test solving of the individuals already acknowledged on our main page for this puzzle. Far be it for me to recount Sanger's career (click here to see how the newspaper of record handled it, and here for an obituary from Nature), but allow me to offer that he revolutionized protein chemistry by determining the amino acid sequence of insulin at a time when most scientists thought that proteins were random heteropolymers of amino acids, then developed methods to sequence complicated RNA molecules, and finally ushered in the modern genomic era by inventing the ingenious "Sanger dideoxy" method for unravelling the order of bases in DNA, a problem that had seemed mind-bogglingly out-of-reach until he showed how it could be solved. For these accomplishments, Sanger received two Nobel Prizes in Chemistry, one of only four individual double laureates in the history of the premiere scientific recognition of modern times.

There was of course a logic to our crossword puzzle construction as a way to pay tribute to Sanger, since his sequencing efforts represent the ultimate in puzzle solving (or decoding). As a graduate student and postdoctoral fellow at The Rockefeller University in the 1970s, I remember talking to several of my professors who recounted being in the room when Sanger first lectured about the insulin work in a simple and elegant manner, showing how each data point brought him closer to the answer. Again, this is second-hand, but I am told that Sanger used some childrens' toy blocks to illustrate the various possibilities. Apparently there came a moment when it became evident to everyone in the room, more or less at the same time, that this was actually going to work, and spontaneous applause erupted. I met Sanger once for sure, and perhaps a second time that may not have been quite as memorable, and was struck by his unassuming demeanor and modesty—an impression supported by others who knew him better, and borne out in the recent obituaries. Finally, my brother Francis reminds me, although he is unable to cite chapter and verse, that at some scientific meeting in the 1960s, our father Michael was, through luck or whatever, Sanger's roommate for the week.

With a bit of finagling, I devised a grid with normal weekday dimensions (15x15) that could include not just Sanger, but also the other three double laureates [Note: all links are to the official Nobel Prize website for the year of each award; once there, additional links provide biographical information—including for co-recipients—and more about the scientific accomplishment(s) being honored].

Other entries connected to the theme include HUMAN_GENOME (21-Across), NOBEL_PRIZES (50-Across), INSULIN_SEQUENCE (56-Across), DNA (32-Across), RNA (43-Across, symmetrically placed with respect to DNA), and the all-important last across entry TWO (68-Across).

We will be writing about the non-theme fill, as well as possible alternative ways to pack in this level of theme material, on a later occasion. For now, we hope you noticed it was a pangram.

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