Biology 466    Unsolved Problems Fall 2013 What James Watson already knew when he got to Cambridge A) He knew that the most important unsolved scientific problem on the verge of being solved was how do genes copy themselves and how do genes encode protein structure? B) He knew Avery, et al. had recently transferred bacterial genetic information by relatively pure chemical extracts ("genetic transformation"), the active component of which they had showed to be DNA (and not protein, as everyone had expected). Most biologists didn't yet believe this result, but Watson's previous teachers did believe it. C) DNA had been isolated from pus in the 1870s, and its chemical structure had long since been determined to be a chain of alternating phosphates and ribose sugars, with a purine or pyrimidine attached to the each ribose, sort of like a side chain. D) Watson had read Erwin Schrödinger's book "What is Life" and taken a course from Max Delbrück, both of whom strongly advocated the conclusion that it wouldn't be possible for genetic mutation rates to be as low as they had been measured to be, unless the information were encoded in some form that required the breaking of rather strong covalent bonds in order to produce a mutation. Thus, protein folding patterns could not be how genes are encoded, because in that case the energy barriers would be so low that mutation rates would be much higher. They calculated this based on thermal vibrations averaging 3/2kT "Three-halves Kay-Tee"). E) Delbrück and Pauling had written papers and (as early as 1940) advocated the opinion that replication of genes should require that they be made of two structurally complementary parts, analogous to photographic positives and negatives, and molding of phonograph records, etc. (this would be as opposed to like-copying-like, of which blueprints are almost the only example) Watson didn't tell Chargaff about Schrödinger's idea or Pauling's +/- theory, or Avery's discovery. (Or maybe he tried to? But Chargaff's mind was closed?) F) Everyone had known for 30+ years that genes were in/on chromosomes, and that chromosomes were made of a mixture of proteins and nucleic acids. But people assumed that genes were made of protein, and that the only function of the nucleic acids was to compensate for the unusually basic proteins in chromosomes. Gee whiz! Why should genetic proteins have so much lysine and arginine? Without so many of these particular amino acids, then chromosome proteins would not be so basic, and need something acidic to complement them. No one seems to have wondered! One major textbook argued that the genes couldn't be in chromosomes, because you can't see tiny microscopic arms and legs and heads and hearts along chromosomes. But people didn't think to answer "Oh, so are there little tiny arms and legs in the mitochondria? or the ER? Which cytoplasmic structures do contain little tiny anatomical organs?" Others argued that the 4 bases of nucleic acids are too few to encode information, ignoring that only three symbols (dot, dash, space) are the basis of Morse code. Any long-chain molecule that has a regular structure is either a straight line, a circle or a helix. Almost always, they are a helix. Logically, there are no other possibilities, if they are regular. (And X-ray diffraction can't work if structures are irregular.) My conclusion is that every member of this class could have done what Watson & Crick did. (If I hadn't been stuck in the fourth grade of Granby Elementary School, in 1952, then I could have done it.) [Granby is between "Harvard Street" and "Oxford Street", and I used to think "Fat chance anyone here has of going to either Harvard or Oxford!]

 

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