Friday, April 30, 2010

Empirical Mechanomeric Development

Mechanomers--functional copolymers such as the proteins and nucleic acids, whether natural or artificial--can be developed empirically.

Mechanomers are developed in nature by variation of monomer order--and therefore of conformation, and therefore of shape, mechanical properties and surface structure, and therefore of function--followed by selection.

Evolution's scale, in numbers of mechanomers and selections and in time, keeps it from being proof that empirical mechanomeric development is practicable; but the development of each individual's antibody complement, and still more each duck's in the egg, and still more the primary immune response, and most of all vaccination and the development and use of antisera and monoclonal antibodies, furnish so many everyday small-scale proofs that proteins performing such more or less simple complexings or molecular recognitions as antibodies can be developed empirically. Enzymes being so many more examples of such complexings can therefore be developed likewise. Proteins performing any equally simple functions or small combinations thereof likewise. Nucleic acids likewise. And mechanomers of other classes likewise.

Proteins and nucleic acids should not be empirically developed, to prevent unwanted genomic introductions. Mechanomer classes mechanomers of which are to be empirically developed should not use naturally-existing monomers, to prevent naturalizations of replicative systems (see below). And mechanomer classes mechanomers of which are to be empirically developed should be non-toxic and biodegradable.

Random polymerization of a mixture of monomers of the different kinds of the appropriate class will produce a mixture of different random mechanomers of the desired class, a random mechanomer stock, and replication or molecular copying of the mechanomers in such stock a mixture of many replicands of each of those mechanomers, a replicated random mechanomer stock. Such stocks will be the fundamental tools of empirical mechanomeric development. And such polymerization and replication will be catalyzed by enzymes, at least one polymerase and replicase respectively, both of another class of mechanomer than that of those being synthesized to avoid unwanted operations upon those enzymes themselves, both operating in the same direction along and continuously upon the growing mechanomer during its synthesis to insure that the replicands have the same conformations as the original, and both themselves empirically developed, in early empirical mechanomeric development (see below).

Proteins generally each assume a single stable conformation, or change between two or three conformations by way and in course of function, but perhaps fewer than one in one billion random amino acid orders specify such well-conformed proteins, and such incidence is taken here to be that of well-conformed mechanomers in random mechanomer stocks. Many mechanomeric functions might be performed by mechanomers which do not assume such conformations (if only because conformed by complexing in course and by way of function), and such incidence will be adequate for the empirical development of mechanomers performing the simplest functions anyway (see below), but development of mechanomers performing more complex functions will require use of some technique(s) for increasing such incidence. Three such techniques, in order of increasing complexity and decrease in synthesis of poorly-conformed mechanomers, are diagonalization (chromatographing random mechanomers along one side of a square medium or matrix and then at a right angle to the original direction until the spectrum lies largely along and is enriched in well-conformed mechanomers along the diagonal, well-conformed mechanomers being more sharply localized in chromatography, such mechanomers extracted and the procedure repeated, using different media), fuzzy replication (using an inaccurate or fuzzy replicase--see below--to replicate an original well-conformed mechanomer, perhaps with a function similar or even identical in part to that desired, and synthesize a random mechanomer stock, analogous to evolution), and splicing (of random or fuzzily-replicated segments into the appropriate areas of otherwise well-conformed mechanomers, analogous to antibody antigen binding site development, followed by replication to insure that those mechanomers assume the conformations they would have assumed upon continuous polymerization and will upon replication for production).

Proteins vary widely in the numbers and orders of the amino acids of which they are composed, but three hundred amino acids is a typical natural protein length and size, and if all proteins with all possible amino acid orders of that length were synthesized, the total mass of protein synthesized would be several hundred powers of ten times the mass of our galaxy. Plainly, if each and every protein function could be performed by only one specific protein with one specific amino acid order, no biological process or artificial procedure could ever develop such. But the evolution of proteins and other mechanomers, and the development and function of antibodies in the body, and vaccination and the development and use of antisera and monoclonal antibodies, all prove not only that mechanomers with different monomer orders can share a given function but that there must be a fantastically high degree of coincidence of function among them. Hundreds out of the millions of different antibodies in the body typically complex with a given antigen, which incidence of one in ten thousand is taken here to be that of such simplest function among well-conformed random mechanomers (taking the restriction of antibody complexing to its antigen binding site alone to cancel out multiple antibody complexing of different parts of antigen). And the greater the number of functions performed by a mechanomer, and the greater their complexities, the lower will be such incidence of such mechanomer, the incidence with two sites performing such functions taken here to be about one in ten thousand squared or one in one hundred million, and the incidence with three one in ten thousand cubed or one in one trillion.

Ten thousand random proteins three hundred amino acids in length will collectively mass a little over six hundred attograms, which stock if replicated to one gram will average about 1.6 quadrillion replicands and one hundred micrograms of each protein, which replicands if of an enzyme each molecule of which produces ten product molecules per second each with the mass of an amino acid will take about four and a half minutes to produce one milligram of such, while one trillion such proteins will mass a little over sixty nanograms, which replicated to one gram will average about sixteen million replicands and a picogram of each, which as such enzyme will take about ten months to produce one microgram of product.

Depolymerases and other enzymes degrading mechanomers of their own class will occur in every random mechanomer stock and make it unstable. Such reactions and enzymes for the most part will be simple ones, the collective incidence of such enzymes in such stocks will be correspondingly high, such stocks will be correspondingly unstable, and such problems will be exacerbated by replication. Random mechanomer stocks should therefore be freshly prepared for empirical mechanomeric development. But if such stock must be stored it should be kept cold, decreasing reaction rates in general; dry, if depolymerization incorporates solvent into the free monomers, as with proteins, amino acids and water; and matriciated (see below), separating most mechanomers in the stock and causing degradative enzymes to preferentially degrade their own replicands.

Matricial empirical mechanomeric development, analogous to antibiotic sensitivity testing, will be the simplest and most common form of empirical mechanomeric development, at its own simplest matriciating (spreading and arraying) a sample of a replicated random mechanomer stock across or through or into a thin layer; overlaying that matrix with any materials and subjecting it to any other conditions needed for the desired function; analyzing the matrix identifying locations in which the desired function is being performed; extracting the mechanomers from those locations for further replication and testing, perhaps by another round of such development (using a different matriciation to redistribute the mechanomers in the sample--see below); and replicating the mechanomer finally selected for its performance of the desired function for production.

Matriciation must be ordered--for example by affine chromatography, chromatographing a sample of a replicated random mechanomer stock using one chromatographic medium and blotting the resulting linear chromatogram into one side of a different medium and chromatographing that a right angle to the first, forming a square or two-dimensional matrix, perhaps itself blotted into a final test matrix and medium--to localize the replicands and effects of each different mechanomer in its characteristic location on the matrix, maximizing concentration of effect and minimizing gestation (time for effect to accumulate to detectability) and analytical sensitivity needed; to perform parallel testing of mechanomers under different or incompatible conditions, using identical matriciations of multiple samples of a replicated random mechanomer stock and comparing mechanomer behaviors at their identical locations from matrix to matrix; to perform parallel recovery of mechanomers from a matrix parallel to a test matrix from which it would be difficult or impossible to recover the tested mechanomers; and to separate most mechanomers and therefore decrease mechanomeric interactions on and in the matrix, causing enzymes degrading mechanomers of their own class to preferentially degrade their own replicands.

Matricial analysis will of course use infrared spectroscopy and nuclear magnetic resonance imaging where appropriate. It will also use orthogonal analysis, by orthogonalization or third-dimensional separation of the matrix, for example by blotting the matrix into one end of and separating its components using a very wide chromatographic column (and orthogonal standards inoculated into the margin of the original square matrix marking in the orthogonal matrix or column planes or bands of interest). But matricial analysis will above all use mechanomeric indication, overlaying the matrix with a previously-empirically-developed enzyme, an indicase, which under some condition resulting from the performance of the desired mechanomeric function catalyzes a reaction causing a color-change on the matrix. Such technique by its analysis at the molecular level, analysis by complexing, cumulative indication as colored indicator accumulates, and ability to use the product of one indicase to trigger another to amplify indication, will render most mechanomeric development amenable to being performed as matricial empirical mechanomeric development. Even though in such development of any mechanomer the function of which is more complex than that of a simple enzyme catalyzing the indicating reaction, false indications will outnumber true.

Mechanomeric evolution, freely mixing unreplicated random mechanomers and monomers with a replicase complexed with a previously-empirically-developed conditional replicase inhibitor which inhibits replication except under some condition resulting from the performance of the desired mechanomeric function, will test the greatest possible number of random mechanomers at a time for a desired function and therefore facilitate the development of mechanomers performing more complex functions occurring more infrequently in random mechanomer stocks. Mechanomeric evolutionary system sizes will be limited by same-class replicase-pair takeovers (see below), and in such development of any mechanomer the function of which is more complex than that of a mechanomer disinhibiting the replicase, false evolutions will outnumber true.

The empirical mechanomeric developmental enzymes and other mechanomers will themselves be empirically developed, in early empirical mechanomeric development:

Replication being a more complex function than and indeed including polymerization, replicases must be more complex and therefore occur more rarely in random mechanomer stocks than polymerases, but cross-class replicase pairs, one from each of two mechanomer classes replicating mechanomers of the other, will evolve in mechanomeric abiogenesis, in which random mechanomers and monomers of both classes are mixed, and such replicases upon encountering one another engage in a more or less exponential course of mutual replication (with a more or less exponentially-increasing heat of replication), with the first such event and pair likely taking over the system. Many such events will produce same-class pairs, which pairs will also limit mechanomeric evolutionary system sizes (see above), and many cross-class replicases produced will be incapable of replicating mechanomers incorporating monomers of all the kinds of the appropriate class supplied, and more or less inaccurate or fuzzy in their replication of the mechanomers they can replicate (such reduced-monomer-set replicases will often be workable until better ones are developed, and such fuzzy replicases will be useful for increasing the incidence of well-conformed mechanomers in random mechanomer stocks--see above).

Once a workable replicase pair is developed, at least one polymerase of each class polymerizing monomers of the other will be developed by matricial empirical mechanomeric development, using random mechanomers synthesized by purely-chemical (non-enzyme-catalyzed) polymerization and then replicated. Such polymerase pairs must operate in the same directions as their classmate replicases, although replicases and polymerases operating in both directions will be developed to develop mechanomers which in the course of synthesis coil in such ways as to bury the ends first synthesized and prevent replication, as well as those which vary in their conformations depending on direction of synthesis.

Finally, sets of mechanomers--growth hormones stimulating cell reproduction and cytodifferentiators converting cells of a sample type to those of others--will be developed and refined and expanded which allow construction of cytopalettes, sets of cultures of cells of different types, for use in matricial empirical mechanomeric developmental matricial overlays in parallel testing of mechanomers for toxicity (including environmental safety). Cytopalettes will include multicytotypic such as neuromuscular junctional cultures. Cytopalettes cultured from cell samples from individual patients will allow the custom development of mechanomeric pharmaceuticals for use in idiotherapies, individual or customized therapies of refractory infections and idiopathic diseases, including cancers. And such cells and tissues will be used for replenishment and replacement, and the engineering of organs for (more or less) autotransplantation.

The utility of empirical mechanomeric development is highlighted by its applications to itself above.


A structure this pretty just had to exist.

James Watson

The foregoing represents a 2,200 word condensation of my 22,000-word informal monograph Random Mechanomers and Mechanomeric Engineering, in progress (barely) and near to completion (hence the sweep of the condensation from elements to advanced techniques).

It was originally posted to the Usenet newsgroups, and sci.research on February 8, 2010, Message-ID: [] .

It is hard to exaggerate the range and depth of impact on technology and especially medicine of such development.

I am seeking and need a grant to finish the monograph.

[See also my two notes on applications from the monograph "Mechanomeric Oncotherapy" and "Empirical Mechanomeric Development and Artificial Photosynthesis of Fuels" ; my adaptation from the first chapter "Proteins" ; and my new "Empirical Mechanomeric Development for Dummies" blog "EMDblog" (in progress).]

Keywords: empirical mechanomeric development, macromolecular nanotechnology, mechanomers, nanobiotechnology


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