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C00002 00002	Josh,
C00003 00003	The PLAUSIBLE Mutation of DNA 
C00016 00004	Relevant Existing Knowledge (the CONTEXT)
C00050 00005	Toward a Theory of what the DNA "Program" has Evolved Into  
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Josh,

The "DNA as Program" analogy  has led me to  an intriguing idea, which  is
described herein.  Because  of the  significance of the  concept (if  it's
true), I am concerned  about how to proceed.   Could you please look  this
over, and suggest a reasonable course to follow (should I collaborate with
X here  at  Stanford,  should  I  go wait  N  years  until  more  data  is
collected,...)?  Knowing how busy you must be, I will appreciate any  time
you can spare  for this.  Incidentally,  if you  want to call  me at  home
(11-12 your time is good), my number is 415-965-1228.

Regards,
Doug

The PLAUSIBLE Mutation of DNA 
-----------------------------

Consider first the analogy between a DNA molecule and a computer  program.
Transfer RNA "swaps  in" the  DNA "program", and  at the  ribosomes it  is
"EVAL'ed" (messenger RNA brings the  required types of "freelist  cells").
The "output" is a polypeptide chain (protein).  The famous "genetic  code"
is the  key with  which triples  of base  pairs are  converted into  amino
acids.  That  is  the  programming  language's  basic  "Print"  statement.
Simple loop termination and other regulatory actions are brought about  by
the program  --  the DNA:  regulatory  genes (which  synthesize  enzymes),
insertion sequences, transposons, phage Mu, and other controlling elements.
The analogy could be extended even further.


The DNA  "program" develops  (is improved  and lengthened)  by  Evolution.
That is, random  changes occur  in the sequence,  manifest themeselves  as
mutated progeny, and are judged by Natural Selection.  The DNA program for
even such a complex organism as Man is assumed to have developed by such a
random generate & test progression.

We in AI know only too well the weakness of doing automatic programming by
random changes  of (and  random additions  of new)  program  instructions.
Certainly it CAN be done, but it  is extremely slow.  The AI answer is  to
add knowledge: add a collection of expert rules for programming in general
and for  the program's  task  domain in  particular.  Code  synthesis  and
transformation is  now  done acording  to  these rules.   While  far  from
complete or foolproof, they are nevertheless far superior to blind changes
in program instructions.

Idea #1:   Can  we  extend  the DNA==program  analogy  by  somehow  adding
knowledge to  the  DNA,  knowledge  about which  kinds  of  mutations  are
plausible, which kinds have been tried unsuccessfully, etc.  That is,  can
we imagine  what it  might mean  to turn  DNA's random  generator  (random
mutations in the  next generation)  into a plausible  move generator?   If
there is a way  to encode such knowledge,  such heuristic guidance  rules,
then we might expect that an organism with that kind of compiled hindsight
would evolve in much more regular, rapid a fashion. The "test" would still
be natural selection,  but instead of  blind generation the  DNA would  be
conducting (and recording) plausible experiments.

What  would  such  heursitics  "look  like";  i.e.,  how  might  they   be
"implemented" in the DNA program?  They  could be written in the  alphabet
of bases, but their interpretation wouldn't be as codons for proteins.  So
someone (e.g., mRNA)  would have to  detect such heuristics  and not  copy
them; or else  at the  ribosome they  would have  to be  skipped over.  At
translation time,  they  would  be  NO-OPs.   At  times  of  reproduction,
however, they would specify allowable (and prevent disallowed) changes  to
be made  in the  new  copy.  I.e.,  they  would sanction  certain  complex
copying "errors".   The "left  hand  sides" of  such heuristics  could  be
almost completely specified  by position  (proximity to  genes which  they
referred to in the rule), and the start of such a heuristic would have  to
be signalled by some special sequence  of bases (much like parentheses  in
Lisp). Each heuristic would have some demarcated domain or scope.

Idea #2:  Nature might  already have become as  good at programming as  we
have.  DNA might have ALREADY evolved from random generate & test into  an
expert program  (expert  at  mutating  itself  in  plausible  ways).   The
recently-observed "introns" are non-coding regions of DNA which just might
correspond to the above heuristics.  Since they are hypothesized by us  to
be heuristics for dealing with  DNA subsequences, and they themselves  are
also DNA subsequences, they (or  at least SOME of  them) might be able  to
modify, enlarge, improve themselves / each other.

What I  conjecture  is  that  Nature  (=  natural  selection)  began  with
primitive organisms and a random-mutation  scheme for improving them.   By
this weak method (random generation,  followed by stringent testing),  the
first primitive introns (heuristics)  accidentally came into being.   They
immediately overshadowed  the  less efficient  random-mutation  mechanism,
just as oxidation quickly dominated fermentation once it evolved.

Each heuristic proposes  a plausible change  (call it C)  in the DNA.  The
progeny which  incorporate C  (call  them PC)  also  get a  new  heuristic
indicating that  that kind  of change  has  been made  and is  good.   The
progeny P which do not incorporate C also get a heuristic added, but  this
one says that a change of type C was tried and failed.  If one group (P or
PC) dominates the other, then that group's new heuristic will have  proven
to be correct.  "False" heuristics die out with the organisms that contain
them.

As the species evolves, so do the heuristics.  One big lesson from AM  was
the NEED for new heuristics to evolve continuously.  Otherwise, as animals
got more and more sophisticated, they would begin to evolve more and  more
slowly (random mutations, or  those guided by a  fixed set of  heuristics,
would become less and less frequently beneficial to the complex organism).
Until Eurisko was conceived,  this would have been  the end of the  story.
We would guess that new heuristics evolve randomly, and in the rare  cases
that they are improvements, they get perpetuated by the progeny which have
them. Thanks to Eurisko, we see that since the heuristics are  represented
just like any other  DNA, they can  work on themselves  as well: they  can
suggest plausible (and/or warn of classes of implausible) changes to  make
in both (i)  the DNA which  synthesizes proteins, and  (ii) the DNA  which
serves as heuristics.

Phenomena  accounted  for  by  this  hypothesis  include:  the  biological
function of introns [heuristics];  the rapid evolution  of man in  general
and his brain in  particular (much more rapid  than one could expect  from
straight random mutation) [heuristic  exploration instead of random  trial
and error]; the ABC result (mutation rate per gram of DNA is not constant,
but rather is proportional to the  lengths of the DNA molecules making  up
the sample) [mutations are mediated by the introns, whose relative  number
increases in  proportion  to DNA  length  (roughly)]; the  Schimke  result
(relearning a  mutation is  much quicker  than initial  learning, and  the
intermediate state  of the  de-learned  DNA is  slightly larger  than  the
original length) [the learning  causes a new heuristic  to form, and  even
after the  mutation  is  forced  to be  un-learned,  the  heuristic  which
summarizes that experience remains]; the  apparent increase in introns  as
one ascends the evolutionary ladder  [more heuristics evolved]; the  large
morphological advances of  some species  (like Man)  compared with  others
(like chimps and  even more dramatically  frogs), even though  at the  DNA
sequence level  they  both advanced  an  equal number  of  base  mutations
[programs with more heuristics can get more done in N cpu cycles].

I called this a hypothesis, and shall now try to justify that claim.  This
has several aspects, which are treated in turn below.  First, the  context
of relevant data is scanned. Next, we  look at at how this hypothesis  can
account for many  unexplained phenomena  in biology.   We scrutinize  what
evidence led to this  hypothesis, rather than some  other, and we  discuss
some of the predictions  made by assuming the  hypothesis.  Many of  these
can  be  tested  experimentally,  and  in  fact  a  few  of  the  proposed
experiments have recently  been carried  out.  Issues  to investigate  are
covered, and  finally  we sketch  out  how  we might  actually  propose  a
plausible  model  for  all  this  (a  formalism,  notation,  and  computer
simulation).

Relevant Existing Knowledge (the CONTEXT)
---------------------------

> Mendelism is accepted absolutely.
  >> That is, we are completely determined by our genetic makeup.
     >>> In particular, by our genetic materials AT BIRTH
     >>> Changing said genetic materials will alter the genetic makeup
          -- and hence the "blueprints" of, the design -- of our offspring



> Evolution in the strict Darwinian sense (i.e., solely via a
  series of random mutations, with Natural Selection providing
  the test for generate&test improvement)  is incapable of
  accounting for the presence of, e.g., Man on earth today.

  >> Certainly, we do not dispute that natural selection operates
     >>> E.g., the adaptation (darkening) of city moths' coloration
     >>> E.g., in societal artifactual systems (academia, politics,...)
  >> Moreover, we concede that simple natural selection could quite
     possibly have preserved each "step" toward Man, had each new
     improvement come along and co-existed with less evolved bretheren.
  >> Certainly, we do not dispute that random mutations occur
     >>> The large number of birth defects each year is sad testimony.
     >>> The "numbers" make it clear that nothing more than random
         genetic mutation is required to account for the phenomenon
         whereby bacteria become resistant to some drug.
  >> Moreover, random mutations could account for each "step" to Man
     >>> A "step" is what Simon would call a "subassembly" -- a stable
         design for an organism which is superior to (hence will be
         selected for over) the previous design of that organism.
  >> We object to the QUANTITATIVE plausibility of the last ">>"
     >>> The order of magnitude of such a "pure hillclimbing"  toward
         Man can be estimated to be as large as 10↑(10↑6) years !!
         >>>> Many of us (e.g., Knuth) see the need for extreme skepticism
              of the doctrine that natural selection of superior random mutants
              can account for Man evolving in so short a time.
         >>>> The mutation rate per gene per generation is around 10↑-7
         >>>> Almost all random mutations are deleterious, or at best neutral.
         >>>> And there is a good chance that even an advantageous new allele
               will be lost (die out before fixation occurs)
               due to fluctuations in its frequency
               in the population as a whole.
     >>> The area of quantitative evolution is currently a hot one
         in the sense that many articles are coming out:
         >>>>> Some recent ones are trying to
               show, e.g., that proteins needn't have evolved too quickly
               (that some of Man's proteins are not much different from yeast's)
         >>>> Cavalli-Sforza: "The evolution of brain size in man turns out to
              be among the most rapid, if not the most rapid, of known
               evolutionary processes."  (p. 692 of The Genetics of Human Populations)
               He then mentions that this enlargement needn't have been gradual, continuous.
     >>> In addition, we must bear in mind that natural selection does not
         tolerate much curvilinear development.
         >>>> I.e., a very complex system (like the double-negative
              repression-repression system for B-galactosidase) would
              have had to evolve in steps EACH of which was a positive
              improvement over the last one.
         >>>> A (straw-man) extreme of this would be to demand that the
               entire system evolve in one huge simultaneous mutation.  
               Simon shoots this down well in his Science of the Artificial.
  >> There are several anomalies in the data about evolution,
      besides the previous one (the doubt about the RATE of evolution)
     >>> Why did man's brain evolve so rapidly?
     >>> Why do some proteins evolve at rates 10 times as slow as others?
         >>>> Older proteins seem to undergo (on average) a smaller no. of changes
         >>>> Some parts of a protein (some amino acids, usually about 5%)
               are absolutely stable (NEVER appear to have undergone substitution,
               even during long evolutionary time periods. (Cavalli p.741)
     >>> Why is the mutation rate per gene proportional to the total length
          of the DNA molecule, not a constant? (ABC paper)
  >> As an analogue, consider the construction of a large program
     >>> Which after all is what DNA is
     >>> One might try to randomly change a program, and to
         (occasionally) randomly add a random new instruction.
     >>> It's feasible to synthesize very short programs by such tactics
         >>>> PW1 by myself (Green et al. AI Memo 1974)
         >>>> Early IBM work on automatic programming (circa 1960)
     >>> This method breaks down rapidly as program size/complexity rise
         >>>> Small random changes in a complex program (e.g., in
              assembly language) are usually fatal, almost never
              beneficial.  
         >>>> For the obvious combinatorial reasons
         >>>> See Fogel et al.'s work on simulated evolution of automata
              >>>>> Note his initial success followed by swamping failure
         >>>> See also the various Cognitive simulations of neonates 
              >>>>> John Burge, MIT efforts, etc.
     >>> Note that we are not demanding the sui generis synthesis of
         a large program all in one step
         >>>> Like a monkey at a typewriter
         >>>> Rather, we are willing to grant as "islands" ANY
              partial programs which are in ANY I/O way superior
              to their parents
              >>>>> They run faster
              >>>>> They use up less space
              >>>>> They can do one more tiny thing than their parents
 *            >>>>> (BUT: what about "They produce better mutant
                     offspring [on the average] than their parents do"?)
              >>>>> "Any I/O way" means any PHENOTYPE difference.
         >>>> Even so, we claim, random mutation is not an effective
              method from which intelligent programs would evolve.
              >>>>> This is the conclusion reached by the above
                    projects which tried such experiments, as well as
                    the combinatorial conclusion.



> Natural selection is accepted completely
  >> Survival of the fittest, in a harsh environment, is the
     sole criterion for judging improvement
     >>> At least in pre-Man ages, which is what we're considering
  >> Natural selection is omnipresent and severe
     >>> At least, for pre-Man ages.
     >>> So, e.g., curvilinear progress is rarely tolerated
         >>>> That is, when a mutation produces an inferior animal
         >>>> But a mutation generations later combines with the
                    first to result in a distinctly superior species.



> Eurisko is assumed to be viable
  >> Not the program, the overall idea
  >> This is a somewhat shaky assumption
     >>> It is underconditioned by DIRECT empirical verification
         >>>> I.e., the program doesn't run yet
     >>> But it is plausible in light of AM and other HPP work
  >> The idea is the conjunction of the following:
     >>> (HPP) Complex tasks call for expert programs
         >>>> To construct an expert program, we must somehow put
              "expertise" into programs.
         >>>> Heuristic if-then rules are a reasonable language in
              which to state (and incorporate) such expertise.
         >>>> In particular, Generate&Test alone is much too weak to give
               adequate performance in complex domains.
     >>> (HPP) Heuristic rules can efficiently guide huge searches
     >>> (AM) The above applies to exploration which is open-ended research
         >>>> At least, in the realm of elementary math theory formation
     >>> (EUR) The above applies to "heuristics" as well as "math concepts"
         >>>> In fact, a body of heuristics can improve and expand "itself" 
         >>>> The most simple. elegant, natural, compact, unifying,...
              way to effect this is merely to represent each heursitic
              as an object in the domain of the body of heuristics
              >>>>> In case the heuristics are like AM's, this means
                    coding each one as a frame-like AM "concept".
              >>>>> So, e.g., any heuristic which can generalize the
                    Defin slot of any concept, can generalize the
                    Defin of any heuristic (including, incidentally,
                    itself!)



> DNA is viewable as a program...

  >> Transfer RNA "swaps in" the DNA "program", and at the ribosomes
     it is "EVAL'ed" (messenger RNA brings the required types of
     "freelist cells").  The "output" is a polypeptide chain (protein).
  >> The famous "genetic code" is the key with which triples of
     base pairs are converted into amino acids.  That is the
     programming language's basic "Print" statement.
  >> Simple loop termination (and other regulatory actions) are
     brought about by the program -- the DNA -- synthesizing certain
     proteins (which we call enzymes) which are capable of interfering
     with the executive control structure (e.g., halting the
     messenger RNA from reading some parts of the DNA, causing it
     to start reading from a new place, etc.)


> ...  but some subroutines serve as-yet unknown purposes.

  >> In higher organisms' DNA, 	there are many long subsequences which
     do not appear to be translated (or even translatable) into
     proteins.  They are called "introns", and their biological function
      is unknown and currently quite a hot topic of speculation.
  >> The percentage of such "non-coding" segments may increase as one
     ascends the evolutionary ladder.
     >>> In prokaryotes, there is no trace of extraneous DNA.
     >>> In yeast, the simplest eukaryotic organism studied extensively,
          there is suggestive evidence for a minute amount of introns.
     >>> In chick albumen, there is a nontrivial amount of introns.
         >>>> This came as quite a shock to researchers, who had previously
               assumed that all DNA was "extrons" -- that is, codings for proteins.
         >>>> The mechanism for ignoring the introns is effected somehow
               by mRNA, which simply cleaves off introns and leaves extrons
               as it's copying, before it moves out to a ribosome.
     >>> [here, add various experimental results about introns]
     >>> Thus there is at present only weakly corraborative evidence for
          my phylogenetic assumption about the increase in introns.



Toward a Theory of what the DNA "Program" has Evolved Into  
----------------------------------------------------------



A reiteration of the central hypothesis:
  DNA has evolved into an expert program, i.e., one with heuristics
  (the introns) for suggesting which (clusters of) mutations are
  plausible. Since the introns are represented exactly the
  same as any other DNA, the introns can refer to (and operate on)
  themselves (in addition to referring to protein-encoding DNA).
  As species evolve viably, the body of heuristics is gradually
  altered (by updating and by the addition of new heuristics) to
  capture the additional history, to compile the new hindsight.

> What does this hypothesis "explain" that old ones don't?
  >> This is partially a set-up, since I carefully chose the
     material on the last page to include just such phenomena.
  >> First, this proposes a use for the introns.
     >>> There must be SOME vital use, if we believe in the
         ubiquity and severity of natural selection.
     >>> It explains why the percentage of introns increases
         with the complexity of the organism.
  >> Second, it explains (better than "Evolution") our presence on Earth today.
     >>> This is not facetious; the key word is TODAY.
     >>> It is a mechanism which may be sufficiently better
         than random mutation so as to lead to Man much quicker.
     >>> It might explain, also, why man's brain evolved so rapidly
          >>>> 500 grams in 500,000 years (20k generations) is a big enlargement
  >>  Third, it could explain various nonuniformities in the rate of 
      sequence evolution
     >>> Though this is not as crucial as the previous two points
          Because (as Wilson, Carlson & White note): The speed at which an
          organism morphologically evolves seems totally unrelated to the rate
          at which his individual proteins (DNA base sequences) evolve.
          "This result raises doubts about the relevance of sequence evolution
           to the evolution of organisms".
     >>> On the other hand, the REASON that some species evolve
          morphologically quickly can be attributed to their effective
          heuristics.  Frogs, e.g., have poor heuristics and have not evolved
          much in eons. WC&W: "Since humans and chimps had a common
         ancestor, much more phenotypic change has occurred in the human lineage
           than in that of the chimpanzee... In spite of having evolved at an
            unusually high organismal rate, the human lineage does not appear
            to have undergone accelerated sequence evolution".  So human
            heuristics are superior to chimps'; even though the evolutionary
            clock has ticked away the same number of sequence mutations,
            the humans have used their time better than chimps, and
            much better than frogs. 
        Anyway, here are some of the other "explainable" nonuniformities:
     >>> Why some proteins evolve at rates 10 times as slow as others, yet
         the rate of evolution is almost constant for proteins within certain
         classes.  As Wilson, Carlson, & White say (Biochem. Evolution, An.Rev.
         Biochem. 1977): "It has been hard to understand why the rate is steady
         within a given class.  As explanations involving pos. natural selection
         did not seem satisfactory, some workers proposed a non-darwinian
         explanation. According to this hyp., the random fixation of selectively
         neutral substitutions is responsible... Recently, a theory involving
         positive selection was proposed to explain the evolutionary clock..."
         >>>> The "explanation" is simply that the evolution is heuristically
             guided.  Uniformity is demanded by randomness, not by intelllience.
     >>> Why some parts of a protein (some amino acids, usually about 5%)
               are absolutely stable (NEVER appear to have undergone substitu-
               tion even during long evolutionary time periods. (Cavalli p.741)
         >>>> We posit that this is the recommendation of some heuristics.
     >>> Why the mutation rate per gene is proportional to the total length
          of the DNA molecule, not a constant (ABC paper)
         >>>> The reason for this is that extron mutations really get triggered only
               rarely by radiation; the most common event is for radiation
               to trigger a change in an intron, which in turn will cause
               a mutation in coding DNA.  Since the relative amount of introns
               is increasing with DNA length, so is the chance of hitting
               an intron, hence so is the rate of mutations per gram of DNA.


> What evidence led to THIS hypothesis, rather than some other?
  >> Again, a set up; see last page.
  >> The empirical necessity of doing automatic programming
     (and complex tasks as a whole) by HPP methods, not weak ones.
  >> The painful way in which I was forced to build Eurisko's heuristics
     as concepts.  I would not have suffered this had it not been
     necessary (i.e., selected for).
     >>> In other words:  a strong analogy to the progression of
         paradigms (at least, MY personal mental world views) in
         AI research (No-Heuristics --> GPS --> Dendral --> AM --> Eurisko)
  >> Such appeals to analogy are not uncommon in molecular genetics
     >>> Enzyme induction mechanisms were debated in terms of locks & keys,
         templates & forms, and other real-world images.
     >>> Adaptors were conceived as analogues of electrical wire or pipe adaptors.
     >>> The analogy of restriction enzyme action to text editing has been fruitful.
     >>> Biologists would not have the HPP, let alone AM, let alone Eurisko,
          designs to draw upon for analogy, hence might take a long time to
          figure out what's really going on (if DNA IS an expert "program").
  >> The simulation of what a discoverized MOLGEN might act like
     >>> In particular, extending the analogy of DNA---Programs
  >> The idea that computer scientists might consciously, intelligently 
     re-design a basis for life (or at least improve on the existing design)
     >>> E.g., writing a program that was cleaner and more powerful than 
         current DNA style
              And then implement that program in wetware
     >>> And the shock of realizing that Nature might already have become
         as good at programming as we have.

> What predictions can be made, assuming this hypothesis?
  >> We want the most radical and unexpected ones, to test the hyp.
     We also want ones for which experiments can be readily executed.
  >> One prediction is that the introns will increase slowly with
     time, within a species, as well as quickly as one crosses
     species boundaries.  
     >>> We should try to measure introns in fossils, if possible
     >>> We should measure amounts of introns vs extrons in as many
         different species as possible, to see if the ratio increases
         monotonically with height on th evolutionary ladder.
         >>>> As pointed out earlier, there is already weakly confirming 
               evidence for this hypothesis.
         >>>> Experiments to test this kind of thing are rapidly becoming
               readily performable, and will be performed.
         >>>> No introns observed yet in prokaryotes
         >>>> A single 14-base non-coding region is spliced out of
               yeast.  This is the most primitive intron.
         >>>> In Drosophila, the 28s gene has several introns and is
               never transcribed.
         >>>> In chick albumen, there are many introns.
  >> We predict that there will be some kind of parenthesization to
      indicate the scope of the introns.
     >>> One way this might appear is if the introns all began with
          a special short base sequence, or two, and perhaps multiple
          copies of that base sequence.  
     >>> Yesterday, Doug Brutlag told me that GAA and GGAA commonly
          occur at the front end of introns.  These may be the [ and (.
  >> Another prediction is that introns might be generally useful.
     I.e., introns from humans might be very useful to mice.
     >>> If we can crack the intron "code" (which may involve
         positional referents and straight history, as well as
         domain-independent heuristics) just a little, we can try
         to transfer some of the introns from an advanced organism
         into a primitive one.  If we succeed, the subsequent
         generations of that organism should evolve MUCH faster
         than they otherwise would have, and probably in the direction
         of whatever the higher organism was.  
  >> A much simpler kind of prediction is that messing with introns
     will affect the % viability of mutant offspring.  This may be one of the
     first experiments to perform, due to its general simplicity.
  >> More convincing would be the following: cause organisms to mutate, and
     then to mutate back, and thridly to mutate in the same way AGAIN.
     We predict that the third mutation will be MUCH faster than the first one.
     >>> Yesterday (Thu., Oct. 12) I asked Doug Brutlag about this particular
          experiment.  Schimke (at Stanford) has done it, and gotten just
          such results.  Also, the length of the DNA increases during the
          initial learning period, decreases during unlearning -- but NOT
          all the way back to its original shortness, and then increases again.
          We guess that the extra residual length is the new heuristic introns.
  >> When would X have evolved?  In particular, when would we
     expect something as good as Man to appear on the scene?
     >>> This is tough to do theoretically.  It might be doable
         empirically, by building a big AI program which simulated
         evolution (not purely random mutation, like Fogel's), and
         which started at some place where SOME introns already
         existed, and which used them to mutate plausibly.
  >> Another prediction is that various kinds of non-random behavior 
     (i.e., mutations occurring in patterns which can be recognized) will
     be noticed at the base-sequence and even at the gene level.
     >>> Brutlag was startled when I asked if this had been observed,
         since that's precisely the phenomenon he's investigating now.

> If the paradigm does seem to be verified, what issues should be investigated?
  >> The foremost problem, of course, is the intron "code".
     >>> We can use hypotheses about unity and simplicity to
         guide our investigations,  and to buoy our spirits that
         the answer is not a convoluted one.
     >>> We will look at the changes when a heuristic is transferred
         to various organisms, and induce what it says.
  >> Perhaps even prior to tackling the code itself, we must
     figure out the mechanism whereby the introns are Evalled.
     >>> Closely tied with this is, of course, the programming
         analogues of the form of the introns.
     >>> If they are IF/THEN type rules, what is the interpreter?
         Is the "IF" part partially or totally specified by position?
         Is the "THEN" part partially or totally a HISTORY of what
         the last (last few?  all past?) modificiations were?
     >>> Are there different types?  Do some types correspond to
         data structures, some to plausibility rules which
         refer to those data structures, and others to interpreters?
     >>> Are the numbers right?  It would be tragic to find
         evidence for the above hypotheses, and yet find that the
         numbers still said man would come out in 100000000000000000 AD.
         Or  the day after bacteria.
         >>>> But it would be more tragic to have conceptualized
              trans-mutation mechanisms, and yet not check to see that
              we had gone far enough (i.e., as far as Nature has gone
              by now) -- and not "too" far.  
         >>>> In fact, it would be justly ironic if the next big
              paradigm shift in AI were motivated by whatever BETTER
              programming ideas Nature has already come up with.
              >>>>> Though this is of course extremely remote a chance!


> Can we propose a plausible model for how this all might work?
  >> Even if it's poorly motivated by empirical evidence, such an "existence
     proof" is quite convincing -- and quite common in genetics.
     >>> Consider Gamow's early scheme for the genetic code.
  >> Let us propose a model which is as close to Eurisko as possible
     >>>  Some sequence of bases function together as a heuristic
     >>>  Each such heuristic H is delimited by a telltale base sequence h
     >>>  Each such hHh group has a particular scope, a domain of relevance
          >>>> Thus, "use a repressor/anti-repressor mechanism rather than
                an induction mechansm" might hold true for a patch of DNA
                which synthesized the organism's most important enzymes.
          >>>>  In lieu of Lisp-like pointers, we suggest some more analogic way
                 of indicating the scope of hHh.
          >>>>  As with AM and Eurisko, a natural way of doing this is to place
                 it just before the relevant referent.
          >>>>  Some base sequences might serve as parentheses to explicitly
                 demarcate the limits of the scope of the heuristic.
          >>>>  Please note that heuristics can have as their domains sets of
                 other heuristics!
     >>>  Each heuristic H consists of a few pieces of information
          >>>> A rating (e.g., how often ANY mutation should be tolerated in
                the section of DNA that comprises the scope of H)
          >>>> A (generalized) change that was tried in the past and worked
                >>>>> What the state was before the change
                >>>>> We presume that the state now is the current state
                       >>>>>> At least after the composition 
                              of all the H's in sequence
                >>>>> We presume that the change was beneficial
                       >>>>>> Else the new animals would not multiply, and the
                               poor heuristics they possessed would 
                               immediately die out (at least, not fix).
          >>>> A (generalized) change that was tried in the past and failed
                >>>>> What the state was before the change
                >>>>> We presume that the change was harmful or lethal
                       >>>>>> Else the new animals would have multiplied, and
                               the wrong heuristics that these old animals
                               possess would have slowly died away.
          >>>> What is the allowable "language" of actions on the
                       right hand (THEN- ) side of each heuristic rule?
                       One typical action might be gene rearrangement.
                       WC&W: "It is notable that rates of evolutionary change
                       in gene rearrangement are unusually high in those groups
                       with high rates of phenotypic evolution and speciation."
                       A related action might be to DUPLICATE a gene;
                       one copy would continue to perform its original function, and
                       the new copy would be available for experimentation.
  >> We should construct a big example scenario of this in action, in detail.
     >>> Notation (in addition to the above) must be developed
                E = a segment of DNA which translates directly into an enzyme
                P = a segment that translates directly into any protein
                E(+P) = a segment that translates into an enzyme that increases
                          the rate at which P is produced in the organism/cell.
                [...] to denote the scope of heuristics
                E(-n%P) + segment translates into enzyme that decreases the
                          production of protein P by about n%.
                s = a start or stop sequence (at front or end of P)
                More notation about functions of proteins (growth, etc.)
     >>> Specify an initial state (for a tiny bit of the nuclein of an organism)
          >>>> The sequences that code for various proteins and heuristics
                E.g., hH1hhH2h[hH3hhH4hhH5hhH6hhH7h[sP1ssP2s]]
                would refer to two protein-encodings, four heuristics relevant
                to them, and two meta-heuristics relevant to those last four.
         >>>> Each Hi and Pi must then be defined in terms of the above notation
               (e.g., we might say that P1 = E(P3)) or in English.
     >>> Go through the simulation
          >>>> Look at the various kinds of mutations that might form, and the
                probabilities of each, and their utilities.  Compare with random.
          >>>> Include here at least a few cases where heuristics, not merely
                protein-encodings, get created and get modified.
          >>>> Also at this stage, we should make some guesses about the
                mechansim for applying the heuristics (for obeying them).  The
                need to come up with a simple molecular explanation is at once
                pressing (for convincing skeptics) and deferrable (since many
                confirming experiments might be done without the precise mechansim
                being understood).