Empirical Mechanomeric Development
John Kennard
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.
< Watson