Most cell structures are formed or synthesized and most other cell functions are performed by the molecules called proteins.
Proteins are polymers, complex chain-like molecules each synthesized by the chemical bonding together or polymerizing of many smaller molecules called their monomers, and furthermore are copolymers, polymers consisting of monomers of more than one kind.
The monomers of the proteins are called amino acids, of which twenty different kinds are commonly incorporated into natural proteins.
The amino acids are small molecules, composed of only ten to twenty-seven atoms each, depending on kind, averaging about twenty, and averaging in mass about 2.35 * 10-22 gram, about one-quarter of one zeptogram (sextillionth of a gram), or 235 yoctograms (septillionths of a gram), about eight times as much as the three-atom water molecule, an oxygen atom single-bonded to each of two hydrogen atoms (an oxygen atom forms two single bonds or one double bond in a molecule, while a hydrogen atom forms one single), the total mass of which is about 2.99 * 10-23 gram, or thirty yoctograms.
Every amino acid molecule consists of a central carbon atom single-bonded to a hydrogen atom, an amino group, a carboxylic acid group and a prosthetic group (a carbon atom forms four single bonds in a molecule, or one double bond and two singles, or two double bonds, or one triple bond and one single). An amino group is composed of a nitrogen atom (which forms three single bonds, or one double and one single, or one triple) single-bonded to each of two hydrogen atoms. And a carboxylic acid group is composed of a carbonyl group or moiety, a carbon double-bonded to an oxygen atom, further single-bonded to a hydroxy or alcohol group, an oxygen atom single-bonded to a hydrogen atom. Such bonds and groups are of course the ordinary molecular bonds and functional groups of carbon chemistry, called "organic chemistry" due to life's taking such advantage of the ability of carbon to form large and stable molecules that most carbon on the face of the earth is or has been part of a living organism. And the amino acid amino and carboxylic acid groups are of course what give it its name.
Every amino acid is identical to every other in the above, regardless of kind, in a nine-atom moiety called here its invariant moiety, composed of its central carbon atom and the hydrogen atom and amino and carboxylic acid groups bonded to it. And an amino acid of one kind differs from one of another solely in the elemental composition (the kinds and number of atoms involved), structure (how those atoms are bonded together) and consequent properties of its prosthetic group.
The invariant moieties of the amino acids incorporated into a protein, minus water of polymerization (the equivalent of one molecule of water is lost for each amino acid incorporated into a protein, the hydroxyl group from the carboxylic acid group and a hydrogen from the amino group), comprise what is called its backbone, an elongated and repetitive structure in which each invariant moiety remnant incorporated forms a unit identical to every other (although of course the end-units each bear a free bonding group unused in polymerization). And the prosthetic groups of those amino acids become protein side-groups projecting from those protein backbone units and that backbone.
Proteins of different kinds and functions vary widely in the number of amino acids of which they are composed. But three hundred amino acids is a modal protein length and size. And a modal protein mass can be calculated based on that length and size by multiplying the average mass of an amino acid by three hundred, and then subtracting the combined masses of the two hundred and ninety-nine water molecule equivalents lost, amounting to about 6.16 * 10-20 gram, about sixty zeptograms, a little over two thousand times the mass of a water molecule. And the corresponding modal protein gram number, the number of such proteins contained in one gram thereof, can be calculated by dividing that mass into one gram, giving about 1.62 * 1019 or about sixteen quintillion such proteins per gram.
Proteins can rotate around their backbone single bonds, and therefore all along their backbones, and consequently twist and coil, but the proteins which perform the functions of the cell generally assume three-dimensional coiled structures or conformations specific to their kinds, stabilized in various ways. For example, attractions between positively- and negatively-charged moieties of molecules form what are called hydrogen bonds, which separately are weaker but collectively can be much stronger than any one molecular bond. Such bonds between nearby backbone units along the protein backbone cause the assumption of winding or helical conformations along the backbone, as well as sheet conformations involving multiple turns and side-by-side runs thereof. Such interactions and resulting conformations are not specific to any particular protein or moiety thereof, since every backbone unit is identical to and can form the same such bonds as any other, and any stretch of backbone could theoretically engage in any such conformation. Slightly more specifically, the backbone units and some side-groups hydrogen-bond water molecules, and proteins tend to coil in such a way as to present such water-soluble or hydrophilic moieties or groups on their surfaces, and hold those side-groups which cannot form such bonds inside, in water-insoluble or hydrophobic cores. But in most of the proteins which perform the functions of the cell, conformation is specified by side-group interactions, which depend on the kinds of side-groups available and the order in which they occur, which depend in turn on which amino acids are incorporated into the protein and the order in which they are incorporated.
That is, protein amino acid order determines protein conformation.
Protein conformation determines protein shape, whether globular, elongated or flattened, and whether solid, indented or hollow; protein mechanical properties, such as whether and how one part of a protein can bend or rotate with respect to the rest; and protein surface structure, the protein’s surface shape and pattern of exposed side-groups and backbone units.
And protein shape, mechanical properties and surface structure determine protein function:
Two proteins or other large molecules of complementary shape and surface charge-patterns upon being brought together will develop multiple attractions including hydrogen-bonds to one another, such fit and collective attraction being called an affinity and such collective bond a complex. Protein complexing is so generally specific in its requirements of complementary shape and charge-pattern as to be described as “lock-and-key”. And protein complexing is a fundamental mechanism of protein function: The conformation-determining attractions and bonds of and within the protein itself can be considered intramolecular or internal complexing. Cytostructural proteins complex with one another to form the internal structural framework of the cell called the cytoskeleton. And every cell contains protein enzymes catalyzing—accelerating—the chemical reactions used by that cell, which reactions would otherwise run too slowly to be of use: Body cells typically each synthesize thousands of different enzymes, and many molecules of each, each more or less specifically catalyzing its specific reaction operating upon its specific substrate(s) or reactant(s) (the phrase "lock-and-key" was first applied to enzyme specificity). And each enzyme catalyzes its reaction largely through, and its specificity is that of, not so much its complexing with its substrate(s) as with its reaction's rate-determining transition state, the highest-energy state through which that reaction must proceed, stabilizing and therefore lowering the energy of that state, allowing lower-energy passage through that state, increasing the probability that a given enzyme-substrate complex will have the energy needed to pass through that state, and therefore, in the cell or other reaction mixture where many such complexes are forming and dissociating, increasing the number of such able to pass through that state and their reactions proceed to completion at any given time, and therefore the overall rate of reaction. In addition, many enzymes catalyze water-sensitive reactions in their hydrophobic cores. More complicatedly, many if not most proteins function by virtue of conformation changes, changing back and forth between two or more conformations in the course and by way of function, a phenomenon called allostery, and complexing is frequently combined in protein function with allosteric conformation changes. Protein complexing of one molecule causing an allosteric conformation change in that protein enabling or preventing subsequent complexing of another molecule is a central mechanism of protein function and control in the cell; for example, some enzymes, including some acting as cell switches, sensors or governors, are activated or deactivated—turned on or off—by conformation changes caused by complexing with or dissociating from the appropriate molecules, some used specifically as signals. And other protein enzymes catalyze the degradation of fuel and use the energy yielded to repetitively alter their conformations and shapes, acting as motors and machines.
Proteins can become damaged in use and need replaced, and indeed are routinely depolymerized and their amino acids reused. Furthermore, proteins need to be passed down from one generation to the next. There is therefore a constant need for new copies of proteins. But proteins are not directly replicated or copied in nature. Instead, the copolymers called nucleic acids, synthesized from monomers called nucleotides, are used as templates to synthesize proteins as well as new copies of themselves. There are two (sub-) classes of nucleic acids, the deoxyribonucleic acids or DNAs or just DNA, and the ribonucleic acids or RNAs. Nucleic acids of each class are synthesized from nucleotides of a corresponding class, the deoxyribotides and the ribotides, respectively, of which there are only four kinds each. Nucleotides are larger and more complicated than amino acids, but every nucleotide molecule is identical to every other of its class in part, regardless of kind, in an invariant moiety bearing two bonding groups of different kinds, and a nucleotide of one kind differs from one of another of its class solely in the composition, structure and properties of a base or base moiety bonded to its invariant moiety, all analogous to amino acids. Nucleic acid strands have repetitively-structured backbones composed of the invariant moieties of the nucleotides incorporated into them minus water of polymerization, and side groups projecting from those backbones composed of those nucleotides’ base moieties, and free end bonding groups unused in polymerization, all analogous to proteins. And just as with proteins, nucleic acid side-group hydrogen-bonding and complexing play central roles in the form and function of nucleic acids in the cell, both perfectly analogously to the proteins, and also in a very specific way used in protein synthesis and nucleic acid replication: The nucleotides of either class consist of two pairs of kinds in each pair of which the base moiety become a side-group when a nucleotide of the one kind is incorporated into a nucleic acid will hydrogen-bond to the other when close enough and at the proper angle. In a nucleic acid which is multiply and sequentially complexed with itself or another nucleic acid the hydrogen-bonded bases or side-groups and the bonds between them are referred to collectively as base-pairs. And two nucleic acids of either class, or one of the one class and one of the other, with complementary nucleotide orders but antiparallel (opposite) directions, can hydrogen-bond base-pair-by-base-pair all along both strands, forming a fully-complexed double strand. DNA generally exists as such double strand, or as a set of such, each of which when wrapped around and compacted with and by proteins for transfer and becoming visible under a microscope during cell reproduction is called a chromosome, and is the very stuff of heredity or biological inheritance, passed from parents to and conferring their biological traits upon their offspring. It is and does so by serving as a permanent record of the amino acid orders of all the proteins synthesized by every cell of the body, every body cell containing the identical DNA(s) (but see the description of B cells below), encoding those orders by means of the genetic code, in which three-deoxyribotide sequences called codons represent amino acids, and sequences of codons called genes represent proteins.
In cell reproduction, the cell divides into two daughter cells, and two DNA double strands or sets thereof, one for each daughter cell, must be synthesized for each such possessed by the parent cell. Simplifying greatly, such DNA synthesis or copying or replication is accomplished by separation of its strands, hydrogen-bonding the complementary deoxyribotides to the newly-exposed ones, and polymerizing the new deoxyribotides into complementary new strands complexed with the old, in what is called, due to each new double strand produced being composed of one old and one new strand, semi-conservative replication.
In protein synthesis, and again simplifying greatly, the DNA double strand is separated in the region of the gene or protein-encoding sequence being used or expressed and the appropriate strand used as a template for the bonding of the complementary ribotides in the transcribing of that gene into in the synthesis of a complementarily-encoded RNA primary transcript, which after post-transcriptional processing including the removal of segments and splicing together of the remainder then serves as a messenger RNA template for protein synthesis, the codons of that RNA complexing with complementary anticodons of transfer RNAs, each of which have been previously bonded to the corresponding amino acids, and which amino acids are then transferred from those RNAs to the growing protein, in the (usually repeated) synthesizing of or translating of that RNA into (usually many copies of) the encoded protein, the process controlled and catalyzed by the protein-and-RNA complex called the ribosome.
Every living thing of every species on our planet uses nucleic acids and the genetic code to synthesize its proteins in transcription and translation, and to inherit and pass on its proteins' amino acid orders and therefore its biological traits in heredity, proving beyond a reasonable doubt that all living things of every species on our planet are related. Since all living things and species are related, we must share a common ancestry. And such common ancestry and later divergence of species is called evolution. Evolution proceeds through mutation or change of trait caused by change of protein caused by change of gene, which last is the only kind of change which can be inherited, those changes which are fatal or otherwise disadvantageous being correspondingly unlikely to be inherited, while those which are advantageous preferentially so, in both negative and positive natural selection.
Evolution is therefore an organism-, cell-, trait- and nucleic-acid-based development of proteins by variation of amino acid order followed by selection.
The leukocytes or white blood cells (called so because they’re not red) called B cells, which synthesize the proteins called antibodies, comprise one exception to the rule that every body cell contains the identical DNA: Antibodies play a central role in the body's immunity to infection, by their complexings with or recognitions of antigen, mostly proteins upon the surfaces of invading microbes. Free antibodies secreted by B cells into the lymph and blood complex with foreign cells and trigger a complex, sequential and cascading biochemical attack by a group of blood proteins called the complement system, ending in among other things the construction of fatal protein pore complexes—holes—in the outer membranes of those cells. Antibodies complex with antigen at a relatively small antigen binding site on the antibody surface comprised of several adjacent runs of protein. During B cell development in early childhood the antigen binding site codon sequences in the antibody gene of each immature B cell are themselves produced by random and imprecise genetic recombinations of short codon sequences from a preexisting pool of such present in DNA. Cells with encoding errors from such recombination are either re-recombined or destroyed, while those which continue to mature encode and synthesize antibodies with antigen binding sites which vary from cell to cell. Such cells undergo further negative selection re-recombining or destroying those which recognize the body's own "self" proteins and cells. And the surviving cells reproduce to form a population of B cells consisting of millions of different B cell sub-populations or clones in the body each clone synthesizing its own specific antibody and all therefore collectively synthesizing millions of different antibodies. Each B cell synthesizes and exposes on its surface something on the order of a hundred thousand copies of the antibody specific to its clone. And such cells upon recognition of antigen are variously stimulated to reproduce, to secretion of free antibodies into lymph and blood, and to other immune activities, including further recombinations, selections and reproductions fine-tuning recognition of antigen.
Antibody development and function are therefore cell- and nucleic-acid-based developments of proteins by variation of amino acid order followed by selection.
Such functional copolymers as the proteins are called "mechanomers" here (distinguishing naturally-occurring mechanomers as "biopolymers" where convenient); the science of mechanomers is called "mechanomerics"; and applied mechanomerics is called "mechanomeric engineering", including "mechanomeric medicine".
Mechanomeric engineering requires some technique for developing mechanomers to perform desired functions, such as enzymes and molecular machines.
And just as proteins are developed in nature by variation of amino acid order—and therefore of protein conformation (coiled structure), and therefore of shape, mechanical properties and surface structure, and therefore of function—followed by selection, so too artificial mechanomers can be developed by selecting those performing desired functions from among random mechanomers, mechanomers with random monomer orders, conformations, shapes, mechanical properties, surface structures and functions, in what is called here "mechanomeric selection".
Evolution's scale, in numbers of mechanomers/biopolymers and selections and across time, keeps it from being proof that mechanomeric selection is a practicable technology.
However, the development of each individual's antibody complement in childhood, and still more such development in the even smaller and faster system of the duck embryo in the egg, and the function of those antibodies, and most of all the medical exploitation of such development and function in vaccination and the medical and industrial development and use of antisera and monoclonal antibodies, all furnish so many everyday small-scale proofs that proteins performing such more or less simple complexings or molecular recognitions as antibodies can be developed by random synthesis followed by selection.
Enzyme function furnishing so many more examples of such complexings, enzymes can therefore be developed likewise.
Proteins performing any equally simple functions or small combinations thereof likewise.
Biopolymers of the other important class of such, the nucleic acids, likewise, within the limitations imposed by their smaller numbers of kind of monomers (and smaller variations in structure between those).
And mechanomers of other classes likewise.
Nucleic acids should in fact not be mechanomerically selected, to prevent unwanted genomic introductions. Mechanomer classes mechanomers of which are to be selected should not use naturally-existing monomers, to prevent naturalizations of replicative systems (see below). And mechanomer classes mechanomers of which are to be selected 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 mixture of many mechanomeric clones, a replicated random mechanomer stock. Such stocks will be the fundamental tools of mechanomeric selection. 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 mechanomerically selected in early mechanomeric selection (see below).
Mass properties of mechanomers significant to mechanomeric selection include (1) incidence of well-conformedness and (2) coincidence and incidence of function among random mechanomers or in random mechanomer stocks; (3) gestation (-time) of mechanomeric function (time for detectable effect to accumulate, taken here to be that of an enzyme); and (4) incidence of degradative enzymes among random mechanomers or in random mechanomer stocks:
(1) Incidence of well-conformedness: 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 will 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 by way and in course of function), and such incidence will be adequate for the selection of mechanomers performing the simplest functions anyway (see below), but selection 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 what are called here "diagonalization", "fuzzy replication" and "splicing":
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.
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.
(2) Coincidence and incidence of function: Proteins vary widely in the numbers and orders of the amino acids of which they are composed, but three hundred amino acids is a modal 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.
(3) Gestation time: 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.
(4) Incidence of degradative enzymes: Depolymerases depolymerizing 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 mechanomeric selection. If such stock must be stored it should be kept cold, decreasing reaction rates in general, and dry, if depolymerization incorporates solvent into the free monomers, as with proteins, amino acids and water. Such stock might also be matriciated (see below), separating most mechanomers in the stock and causing degradative enzymes to preferentially degrade their own replicands, and even bound after matriciation to some matrix, fixing the mechanomers in place and completely halting such degradation.
What is called here "matricial mechanomeric selection", analogous to antibiotic sensitivity testing, will be the simplest and most common form of such selection, 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 replicated random mechanomer matrix with any materials and subjecting it to any other conditions needed for the desired function; analyzing that 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 selection (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 as noted above to separate 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 what is called here "mechanomeric indication", overlaying the matrix with a previously-selected enzyme, called here an "indicase", which under some condition resulting from the performance of the desired mechanomeric function catalyzes a reaction converting a substrate, called here an "indicator", causing a color-change on the matrix. Such indicase will be readily developed by overlaying a replicated random mechanomer matrix with indicator, then subjecting that matrix to the desired condition, and noting where indicator was not converted and no color-change took place until that condition was applied. Mechanomeric indication 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 selection amenable to being performed as matricial mechanomeric selection. Even though in such selection of any mechanomer the function of which is more complex than that of a simple enzyme catalyzing the indicating reaction, false indications by any given indicase will outnumber true, making advisable the development and simultaneous use of multiple indicases in such selection, and selecting only from regions on the matrix where multiple indication is taking place.
What is called here "mechanomeric evolution", freely mixing unreplicated random mechanomers and monomers with a replicase complexed with a previously-selected what is called here "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 selection of mechanomers performing more complex functions occurring more infrequently in random mechanomer stocks. Such conditional replicase inhibitor will be readily developed by first developing an indicase which converts colored indicator to colorless, then overlaying two parallel random mechanomer matrices with monomers, replicase and that indicase, subjecting one such matrix to some condition resulting from the desired function, and observing where in the latter indicator color persists. Mechanomeric evolutionary system sizes will be limited by same-class replicase-pair takeovers (see below), and in such selection of any mechanomer the function of which is more complex than that of a mechanomer disinhibiting the replicase, false evolutions will outnumber true.
The enzymes and other mechanomers needed for mechanomeric selection will themselves be mechanomerically selected, in what is called here "early mechanomeric selection":
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 what is called here “mechanomerogenesis”, 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, note, 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 selected, at least one polymerase of each class polymerizing monomers of the other will be selected by matricial mechanomeric selection, 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 selected to select 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 selected and refined and expanded which allow construction of cytopalettes, sets of cultures of cells of different types, for use in matricial mechanomeric selective 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 selection of mechanomeric pharmaceuticals for use in idiotherapies, individual or customized therapies of refractory infections and idiopathic diseases, including cancers (see below). And such cells and tissues will also be used for replenishment and replacement, and the engineering of organs for (more or less) autotransplantation.
The utility of mechanomeric selection is highlighted by its applications to itself above in mechanomerogenesis and other early mechanomeric selection (including the selection of cytopalette mechanomers), mechanomeric indication, and mechanomeric evolution.
There are, of course, many other relatively easily foreseeable applications for such technology, in particular with regard to medicine and industry.
Mechanomers specifically toxic to microbes of a given species but not to those of other species or to humans will be mechanomerically selected. At its simplest, such selection will take the form of parallel matricial mechanomeric selection: overlaying a set of parallel identical replicated random mechanomer matrices with, respectively, a culture of the microbes in question, cultures of microbes of as many other species as practicable, both human commensals (to avoid for example disturbing normal human gastrointestinal microflora and possibly facilitating fulminating toxic overgrowths) and a selection of environmentally-significant species, and cytopalette cultures of as many different human cell types from as many different humans as practicable; observing for regions where on the first matrix the microbial cells die but on the others no cells do, deaths signaled by mechanomeric indication for greatest sensitivity; extracting the random mechanomers from those regions from yet another parallel matrix; re-matriciating the mechanomers from each such region using different media to separate them; and repeating, until a specific and effective antimicrobial is selected. Multiple agents should be selected to overcome microbial resistance to any one such and to reduce the amount of each such agent needed and therefore any side-effects therefrom. And note that such selection of antimicrobials will enjoy even greater flexibility than microbes themselves do in their developments of resistances to antimicrobials, since it will be limited neither to starting from naturally-existing mechanomers nor to mechanomers of naturally-existing classes. Furthermore, it will be much faster than the microbial development of antimicrobial resistance.
Mechanomers preventing viral destruction of cells will be mechanomerically selected. At its simplest, such selection will take the form of parallel matricial mechanomeric selection: overlaying a set of parallel identical replicated random mechanomer matrices with, respectively, cytopalette cultures of as many different human cell types from as many different humans as practicable, and cultures of human microbial commensals (to avoid for example disturbing normal human gastrointestinal microflora and possibly facilitating fulminating toxic overgrowths); overlaying the human cell matrices with a solution of the virus in question; observing for regions where on the human cell matrices the cells do not die but on the microbial matrices no cells do, deaths signaled by mechanomeric indication for greatest sensitivity; extracting the random mechanomers from those regions from yet another parallel matrix; re-matriciating the mechanomers from each such region using different media to separate them; and repeating, until a specific and effective antiviral is selected. And just as with the mechanomeric selection of antimicrobials, multiple agents should be selected to overcome viral resistance to any one such and to reduce the amount of each such agent needed and therefore any side-effects therefrom, and such selection of antivirals will enjoy even greater flexibility and speed than viruses themselves do in their developments of resistances to antivirals.
Cytopalettes cultured from cell samples from individual patients will allow the custom selection of mechanomeric pharmaceuticals for use in idiotherapies, individual or customized therapies of refractory infections and idiopathic diseases, including cancers.
Mechanomers toxic to cancer cells but not to cells of their parent (or other normal) cell types will be mechanomerically selected, for the individualized mechanomeric oncotherapies necessitated by the individualized nature of cancers. Cancer cells are mutated cells, with at least one and usually multiple DNA abnormalities and consequently abnormal messenger RNAs transcribed from those DNAs and abnormal proteins translated from those RNAs, and the differences between such DNAs, RNAs and proteins and their normal versions will allow the mechanomeric selection of mechanomers which are toxic to such cells only (e.g., lethal enzymes activated by complexing with such abnormal proteins only). At its simplest, such selection will take the form of parallel matricial mechanomeric selection: overlaying a set of parallel identical replicated random mechanomer matrices with, respectively, a culture of the cancer cells in question, perhaps a culture of the parent cell-type of that cancer, and cytopalette cultures of as many other (normal) cell types generated and cultured from the patient as practicable; observing for regions where on the first matrix the cancer cells die but on the others none do, deaths signaled by mechanomeric indication for greatest sensitivity; extracting the random mechanomers from those regions from yet another parallel matrix; re-matriciating the mechanomers from each such region using different media to separate them; and repeating, until a set of individualized antineoplastic or oncotherapeutic mechanomers is selected. It is unlikely that even with the use of multiple oncotherapeutic mechanomers that all the cells of a cancer will be killed, and indeed some if not most cancers more or less steadily and rapidly mutate, so the mechanomeric oncotherapies of such cancers will therefore involve not only multiple mechanomers but also one or more extra passes or rounds of such multiplex therapy, as the cancer reoccurs to be re-sampled and a new set of oncotheraputic mechanomers selected to deal with it, with the majority of such cells destroyed by each pass, and a genetically-different minority left (if any) to begin again (note that even if not directly destroyed, the cells of such cancer held in check long enough should become ever more mutated, function ever more poorly, with ever greater numbers of its cells being fatally mutated, or exhibiting mutated proteins detectable and those cells therefore destroyed by the immune system, in what might be called "neoplastic burnout").
Cytopalette cells and tissues will be used for replenishment and replacement of tissues lost to injury or illness, including senescence, as well as the construction of organs for (more or less) autotransplantation.
As far as industrial applications of mechanomeric selection go, many expensive and/or toxic and/or otherwise hazardous industrial chemical catalysts will of course be replaced by mechanomerically selected enzymes. Such enzymes will catalyze many reactions at lower temperatures and pressures than at present, lowering energy use and cost, and many others in water rather than more expensive and/or toxic and/or otherwise hazardous solvents. Such catalysis due to enzymatic specificity will furthermore reduce side-reactions and increase the efficiency and economy of such reactions. And it will also allow new reactions to be developed and run as well, such as higher-order ones involving greater numbers of reactants at a time.
Most importantly, mechanomerically selected enzymes will afford artificial photosynthesis of fuels, organic chemical industrial feedstocks, and bulk nutrients such as cooking-oils and sugar, reversing the dumping of crustal carbon into the atmosphere over the last several centuries.
Thus the first glimpses of the new medicine and photosynthetic economy that will be afforded to us by mechanomeric selection.
The above, the fourth version of an analysis begun in 1992 as a private study of senescence and gerontotherapy, was based principally on two secondary sources:
Hendrickson, James; Cram, Donald; and Hammond, George. Organic Chemistry. Third Edition. New York: McGraw-Hill Book Company, 1970. The classic introduction to the classic science.
Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; and Walter, Peter. Molecular Biology of the Cell. Third/Fourth Editions. Garland Science, 1994/2002. A tidal-wave of information on the core functions of the biopolymers.
Any errors in fact or analysis are of course the present author’s.
Keywords: antibiotic, antisenescent, antiviral, bionanotechnology, engineering, enzyme, mechanomeric selection, mechanomers, medicine, MeSe, molecular machine, nanotechnology, oncotherapy, artificial photosynthesis, virotherapy