The task Dr. Ressler set himself was merely — and only he could have thought "merely" — to capture the enigma machine that tweaks this chromosomal message into readability. Did he believe that nothing was lost in translation as signals percolated up from molecules in the thread into him, that brain, those limbs, that hurt, alert face? Searching for his own lexicon required faith that the chemical semaphore could serve as its own rosetta, faith that biology too could be revealed through its particulars. Faith that demonstration could replace faith.
It grows like a crystal, this odd synthesis of evolution, chemistry, and faith, spreads in all directions at once, regular but aperiodic. By Ressler's birth, enzymes — catalysts driving the chemical reactions of metabolism — were identified as proteins. The structure of proteins — responsible for everything from the taste of sole to the toughness of a toenail — strikes me as ridiculously simple: linear, crumpled necklaces of organic pearls called amino acids. What's more, the protein necklaces directing all cell processes consist of series of only twenty different amino acid beads.
It seems impossible: twenty can't be sufficient word-hoard to engineer the tens of thousands of complex chemical reactions required to make a thing live. But lying in bed under my arctic nightlight, carrying out the simple arithmetic, I see how the abject simplicity of protein produces more potential than mind can penetrate. A necklace of only two beads, each in one of twenty colors, can assume any of four hundred different combinations. A third bead increases this twenty times — eight thousand possible necklaces. I learn that the average protein necklace floating in the body weighs in at hundreds of beads. At that length, the possible string combinations exceed the printed sentences in man-made creation. Room to grow, in other words.
The protein bead string folds up, forms secondary structures determined by its amino acid sequence. The shape of these fantastic landscapes, fuzz-motes as convoluted as the string is simple, gives them their specific, chemical power. Their jungle of surface protrusions provides — like so many dough forms — niches for other chemicals to assemble and react.
But if these cookie cutters — in countless possible fantastically complex shapes — build the body, what builds the builders? The answer appalls me. The formula for the builder molecules as well as its implementation are contained in another long, linear molecule. This time the beads come in only four colors. It says something about my progress in scientific faith that I accept the calculation showing that the possible combinations in one such foursquare informational molecule exceed the total number of atoms in the universe.
But I hang up on the idea of such a linear molecule encoding a breathing, hoping, straining, failing, aging, dying scientist. I find as I read that I'm in good company. If I still ran the Quote Board, I'd use tomorrow that gem of Einstein's when meeting Morgan and hearing of his project to mechanize biology:
No, this trick won't work— How on earth are you ever going to explain in terms of chemistry and physics so important a biological phenomenon as first love?
But I no longer run the Quote Board. I run nothing now except the Jan O'Deigh Continuing Education Project. And for that, I have only more history. When counting aminos fails to put me to sleep, I charm insomnia by reading Beadle and Tatum's 1940 work on the bread mold Neurospora. Only seventeen years old when Ressler got his brainstorm, it must have read like a classic to a student raised on it. While the world once more indulged its favorite occupation, Beadle and Tatum dosed mold with X-rays to induce mutations. Raising thousands of test-tube strains, they produced mutants that could no longer manufacture required nutrients. Mutated chromosomes failed to produce necessary enzymes.
With an excitement that penetrates even the sober journal account, they crossed a mutant that could no longer make enzyme E with its normal counterpart. Half the offspring had the mutation and half did not. Enzyme production precisely mirrored Mendelian inheritance. One gene, one enzyme. Each time I read the conclusion, I hear his perverse question: "What could be simpler?"
A unique gene, coding for a unique enzyme: Cyfer inherited as dogma what actually arose only through recent, bitter debate. The limited informational content of DNA — the four bases adenine, guanine, cytosine, and thymine — did not seem adequate to build the fantastically varied amino acid necklaces. For some time, the size of DNA was underestimated, and even after the enormous molecular weight was correctly determined, many scientists believed that the four bases followed one another in repeating order. Redundant series carry no more information than a news program repeating, "Earlier today, earlier today__"
DNA was long rejected as the chromosomal message carrier. Some researchers believed that proteins themselves were the master blueprint, even though every protein would require others to build it. Avery blazed the trail out of confusion. His 1944 paper showed that the substance transforming one bacterial strain to another was not protein but DNA. Inheritance was rapidly being reduced from metaphor to physical construct. DNA was a plan that somehow threaded raw amino acid beads into proteins. These protein chains in turn catalyzed all biological process. Cyfer's question — the coding problem — was how a long string of four types of things stood for thousands of shorter, twenty-thing strings.
Before the problem could even be posed, scientists had first to determine a structure for DNA that fit the evidence. The structure fell the year Ressler attained legal adulthood, one of the most celebrated solutions in science. X-ray diffractions of crystalline nucleic acid suggested a helix. The beautiful Chargaff Ratios demanded the amount of adenine equal that of thymine, guanine equal cytosine, and G + A equal C + T. DNA presented too many structural possibilities to be cracked by standard organic analysis. By starting with the constraints in Franklin's and Wilkins's data, Watson and Crick tinkered with cutouts until the shoe dropped. They hit upon the double helix, where complementary base pairs — G pairing always with C, A always with T — form the spiral rungs.
Temperament, coded in long strings of base pairs, plays a big part in any interpretation of data. The full ramifications of the model were not quickly grasped. It followed neatly that chromosomes were just supercoiled filaments of DNA. Mendel's genes were simply sections of chromosome, a length of spiral staircase— say ten thousand base-pair rungs spelling out auburn hair. But using four letters to convey the content of all living things seemed like transmitting every Who's Who of this century in staticky dots and dashes across a copper filament.
How was the message read? How to determine the language of the cipher? Understand that question and I've understood him. Dr. Ressler, receiving intact the work of the structurists, trained his temperament on the smallest end of the genetic spectrum, the connecting link. The task given him was to determine how twin-helical sequences of four bases
strung amino acids into enfolded protein:
… threonine-valine-tryptophan…