The inert shape of this enzyme has a binding site that fits substance A. The active shape has a site matching B as well as materials C and D that it transforms into product E. If A grabs the molecule first, it locks it into inert shape, eliminating those sites that accept the catalyzable materials. The enzyme is switched off, C and D can't bind, and manufacture of E stops. But if B first binds to the enzyme in active form, it locks the molecule into a shape with C and D's sites intact. The faucet is held open; the enzyme joins C and D into E so long as supplies of C and D exist.
Ressler's magic Boolean circuitry begins to emerge. The presence of A inhibits the manufacture of E; B promotes it. None of the compounds reacts with the enzyme itself; the machine remains unchanged except for switching on or off, always capable of switching back if the splint-substances detach. Even wilder: the inhibitors, promoters, and inputs, binding to independent sites, need have nothing to do with one another. A, B, C, D, and E can be anything at all. In theory, any chemical can be made to inhibit or promote the formation or degradation of any other. The effect can even be nonlinear; multiple binding sites on an enzyme could cause small amounts of compound to have enormous effects on the synthesis of others.
Here it is, my escape act from chemical necessity. Microcircuitry I can't begin to map: a single allosteric enzyme made up of a few hundred amino acids, weighing less than a million billionth of a gram, accepting multiple, graded inputs and producing nonlinear output, a free-floating if-then program. It smacks of religion to me.
But the conjuring act hasn't even begun. Link the logical feeds of an allosteric circuit together, and the molecule virtually lives. E, the reaction product, can be the same as A, the inhibitor. Every successful catalysis then shuts off the switch. Or E, used up by the body, might degrade into promoter B, ensuring that new E is created whenever old stock is expended.
With self-regulating feedback, the enzyme becomes its own economy, gauging supply and demand in the chemical soup, even acting to adjust these. I enter loops, linked regulatory patterns more ingenious than theistic design. One molecule's manufactured product can inhibit or promote another's. Two enzymes activate each other in conjunction or opposition. Metabolic pathways branch and conjoin, one enzyme setting off two others, or two in tandem combining to shut down a first. These and, or, and not operations create a complete prepositional calculus.
Coordinated microprograms capable of changing their own environment, able to spring into production modes within an instant of encountering a trigger, create a cybernetic network powerful enough to initiate the impossibly articulated behavior of the composite cell. Q: Is the tracery of microprogramming networks too complex to have arisen through guided chance? Q: Is it complex enough to account for the autonomy that high-level enzyme byproducts — Ressler, Todd, myself — all suffer from?
I've started four times today, on four separate sheets — what? Nothing. Trivial message strings going no farther than Dear Franklin. Even the adjective is problematic. After months, I have the man's address. I have a world of things to tell him. Nothing stops me. I want to write. But even today — Caesar crosses Rubicon, 49 B.C. — I can't. I won't. English doesn't have the modality to say what's keeping me. Writing him is fine, but words are out. A is too functional, B too forgiving. C and D are transparent excuses for E, which I will never bring myself to say to him again.
I own his mailbox, the lookup table to the one spot where he can be reached. If I could finish a fifth sheet, seal and mail it without reading… I could; I want to. The first letter of the first sentence, and I waver from one urge to the other. I am truly stochastic, indecisive. Do all inputs, computed, already drive me to one course or the other, or can they still be interfered with by some messy conglomerate circuit, me?
I try on Laplace's old dream — to solve the world through giant inference engine. Ressler, alert, talkative as I had never before seen him, racing through the data stacks looking for our place to cut, cracked a joke about the final triumph of the reductionist program. "NASA's eyes in the sky determine the vectors on every molecule of atmosphere. They feed all these numbers into a Cray, and the animal pounds away, megaflops, on a simulation that knows everything about adiabatic cooling, turbulence, vapor pressures, topography, solar radiation. The machine assembles and delivers a perfect prediction of tomorrow's weather. Only it takes two days to run."
The problem is irresistible. Do all my active enzymes plus the running average of the chemical soup they find themselves in, the jungle of bioeconomy (vast, uncatalogued tracts of electrochemical memory, mine and earlier), all the stimuli bombarding me from outside — the January sun's false springs out my window, the glass of water at my elbow (complete with Brooklyn reservoir heavy impurities), the feel of the keys under my fingers — do all these independent effectors sum to one unique output: write him or not? They couldn't sum to more than one outcome. What would it even mean to say the choice, the final cybernetic weighing were left open? Open to what? Whom?
I must be asking the question wrong. Any outcome, once reached, must have been decided by something. The sort of freedom I am talking about — Dear Franklin, Where are you? When can I see you? How long you have been away! Come home — must be constraint by another name. Constraint that jumps some complexity threshold. The molecules I look for need not be capable of autonomous behavior; the word, when pushed, probably has no meaning. But are they enough, in themselves, to escape the determinism of physical vectors? Do these microprograms, once fired up, always run the same way, water down an arroyo? Or can they self-determine, self-modify, rewrite their own program listings?
They can. Allosteric enzymes are themselves synthesized. The microtransistors are drawn up, tailored, detached, and sent into the fray by a macroprogram, the nucleotide sequence — semantic bursts of DNA thread. Worker bees, assembled by the queen in her hive, these hatchetmen, day laborers, have the critical ability to apply their logical toolboxes back on the master program. Allosteric proteins can bind to and influence DNA, inhibiting or promoting the synthesis of allosteric enzymes themselves. I stare at purpose, at the molecular level. The running program — DNA synthesizing enzymes — creates and executes subroutines that double back, influence the way the master program executes, cascading into new subroutines, run-time solutions.
To the best of my metaphoric understanding, it goes like this. Codons along a stretch of DNA direct the sequencing of amino acids in a protein. This sequence constrains the lint-ball molecule to adopt one of two or more possible shapes. Held in one shape by an attached brace, its personality — the lure of its binding sites— is inert. But when that jamb is removed, the protein recoils, takes on a new surface. Part of that switched-on surface attaches to a segment of DNA, switching oíf that segment's instructions. The segment of code temporarily patched out could even be the one manufacturing the binding molecule itself. The substance that switches the protein's code-modifying abilities on and off theoretically could be anything, even the by-product of enzymes manufactured on that or other DNA segments. The master control and its agents combine to alter their own combined behaviors.
One allosteric enzyme, working by itself, is already a formidable machine, reactively linking unrelated substances. Thousands of them, joined into branching, judging, regulating feedback networks, can just about account for the numbing inventories, the shifting assembly lines that run the corporate cell. With meta-programming — the ability of the central network to reset even its own switches — the last constraints of the hardwired universe are shed. The field is broken wide open. Anything can happen, and does.