Evolution; a feeling for the organism

[From Bill Powers (940811.1000 MDT)]
RE: evolution

A couple of years ago, Mary brought home a book:

Keller, E. F. (1983); _A feeling for the organism: the life and work of
Barbara McClintock_. (San Francisco: W. H. Freeman)

Barbara McClintock was a cell biologist who studied the genetics of
maize. What she got a Nobel Prize for in 1983 was discovering the
transposablity of elements of the genetic structure, a discovery made in
late 1940s and early 1950s, and which was largely ignored because it
went against accepted ideas. What she didn't get a Nobel Prize for
(according to this feminist biography), but should have, was being a
woman in a science dominated by male geneticists who apparently believed
that a woman was genetically incapable of creating a scientific
breakthrough. I think Keller was partly right, but that the real problem
was much deeper than that.

I now have a strong suspicion that McClintock discovered more than she
knew: she had found the essential components of negative feedback
control systems that govern the activity of the genome. In fact, listen
to McClintock writing in 1962, 21 years before her Nobel Prize:

    In _Year Book 60_, parallels were drawn between gene-control systems
    in maize and those in bacteria. In both organisms, the comparable
    systems are composed, basically, of two genetic elements: an
    "operator" element, located adjacent to the structural gene(s) and
    directly controlling genic activity; and a "regulator" element that
    in turn controls the functioning of the operator element. Each
    operator responds only to a specific regulator. Therefore, each
    operator with its corresponding regulator represents a gene-control
    system. In bacteria, the position of the regulator element on the
    chromosome is not the same in all examined systems: it may be
    located either near by or at a distance from the operator. Probably
    the control systems in maize express similar topographical
    relationships; evidence supporting that probability will be
    presented here.

Note in passing: what a writer! To go on:

    In maize, the controlling elements of a system are transposable
    [WTP: meaning movable, not that they trade places]. Therefore,
    different genes may come under control of the same system, or the
    same gene under the control of different systems. Inception of
    control of gene action by a particular system sometimes occurs when
    the operator of the system is inserted near the locus of the gene,
    the regulator element being located elsewhere in the chromosome
    complement. At other times, inception of control is associated with
    the appearance of the regulator near the locus of the gene. In each
    example that has been examined adequately, however, a clearly
    expressed two-element system has subsequently arisen, the operator
    element residing near the gene locus and responding to the regulator
    element, now located elsewhere in the chromosome complement.

The foregoing is from p. 430 of

Moore, J.A. (Ed) (1987): _The discovery and characterization of
transposable elements: The collected papers of Barbara McClintock (New
York: Garland). The following quotations are also from that source.

The final paper in the collection was published in _Science_, _226_,792-
801, 16 Nov. 1984, when McClintock was 82 years old (Born in 1902, she
died at the age of 91, before I learned of her, dammit). The title of

the paper is "The significance of responses of the genome to a
challenge." It starts like this:

    There are "shocks" that a genome must face repeatedly, and for which
    it is prepared to respond in a programmed manner. Examples are "heat
    shock" responses in eukaryotic organisms and the "SOS" responses in
    bacteria ... Some sensing mechanism must be present in these
    instances to alert the cell to imminent danger, and to set in motion
    the orderly sequence of events that will mitigate this danger.

Note: this requires that some sensed variable actually has begun to
change. Also note: most of the changes of which McClintock speaks are
_inheritable_, meaning that the control systems are operating across
generations. I have yet to run across any mention of "random mutation"
in my readings of McClintock.

    But there are also responses of genomes to unanticipated challenges
    that are not so precisely programmed. The genome is unprepared for
    these shocks. Nevertheless, they are sensed, and the genome responds
    in a discernible but initially unforseen manner.

The significance of these ideas for "genetic reorganization" and PCT-
type control are obvious. Near the end of the paper:

    It was these various effects of an initial traumatic event that
    alerted me to anticipate unusual responses of a genome to various
    shocks it might receive, either produced by accidents occurring
    within the cell itself, or imposed from without, such as virus
    infections, species crosses, poisons of various sorts, or even
    altered surroundings such as those imposed by tissue culture. Time
    does not allow even a modest listing of known responses of genomes
    to stress that could or should be included in a discussion aimed at
    the significance of responses of genomes to challenges.

Barbara McClintock published her first paper, as junior author, in 1926,
the year I was born. She wrote an introduction to her collected works
near the end of her life; in it she traces not only the evolution of her
ideas and discoveries, but a history of a sort with which we in PCT are
rather too familiar:

    The study of insertions of a Ds into known gene loci had progressed
    sufficiently by 1950 to warrant publication in a journal with a wide
    readership [WTP: Proceedings of the National Academy of Sciences].
    The report was titled "The origin and behavior of mutable loci in
    maize." It was clear from responses to this report that the
    presented thesis, and evidence for it [WTP: !], could not be
    accepted by the majority of geneticists or by other biologists.
    Genetics was still in an unformed state compared to the rapid
    changes that occurred subsequently in the 1950s and 1960s, and there
    was no clear notion of the nature of the gene. It remained a
    hypothetical unit until proven otherwise. A long report in the _Cold
    Spring Harbor Symposium_ for 1951 represented a second attempt to
    present the "mutable loci" story as it was progressing at Cold
    Spring Harbor... The response to it was puzzlement and, in some
    cases, hostility. A third attempt to support the thesis of the
    origin of mutable loci in maize appeared in 1953 in the widely read
    journal _Genetics_... It was titled "The induction of instability
    [WTP: !!] at selected loci in maize." This article appeared before
    copying machines practically eliminated requests for reprints. At
    the time, reprints were distributed to a selected few, and to others
    on request. In this instance I received a total of only three
    requests for this reprint! By then I had already concluded that no
    amount of published evidence would be effective. As a consequence,
    beginning in January, 1949, those projects that had reached a state
    allowing conclusions to be drawn from them, or were in need of data

    assembly or comment, were treated to an unpublished written account,
    with tables of data, diagrams when needed, and a discussion of the
    significance of the findings. Only the highlights of these studies
    were reported in the annual Year Books of the Carnegie Institution
    of Washington.
    ...
    In retrospect, it appears that the difficulties in presenting the
    evidence and arguments for transposable elements in eukaryotic
    organisms were attributable to conflicts with accepted genetic
    concepts. That genetic elements could move to new locations in the
    genome had no precedent and no place in these concepts. The genome
    was considered to be stable, or at least not subject to this kind of
    instability. A further difficulty in communication stemmed from my
    emphasis on the regulatory aspects of these elements. In the mid-
    1940s there was little if any awareness of the need for genes to be
    regulated during development. Yet it was just this aspect that
    caught my attention initially...

    Only now, more than forty years after the discovery of transposable
    elements, are we beginning to understand enough about the ways they
    can affect genes to decipher some intriguing new aspects of gene
    control from their study.

I can imagine the sorts of comments geneticists made, if they were
anything like the things psychologists and others have said about PCT:
"Well, I'm not really interested in corn."

It is utterly amazing to me to see how science itself can get in its own
way, by too loyal an acceptance of what is commonly believed. Every
science, even the holy science Physics, suffers from this human
reluctance to re-examine the known. Most scientists would far rather
boast about the accomplishments of the science whose glorious successes
reflect favorably on all its practitioners, and most of them treat any
true advances in their science as threats to be deflected and
neutralized by any means possible, fair or foul.

···

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McClintock gives a tantalizingly clear picture of where and how control
systems might exist in the genome. The "operator" element seems to
correspond to an output function, the "regulator" element to a
combination of input function and comparator. Of course when McClintock
says that the operator element "controls" the gene, she is reflecting
the usage which grew up without any understanding of control systems.
The proper way to say this is that the operator _varies_ the activity of
the gene. What is controlled is whatever is being sensed by the
regulator element and simultaneously affected by the genic activity.
Clearly, varying a given genic activity can serve to control variables
either near to the gene or far from it. The placement of the regulator
element and its specific sensitivity determine what is controlled and
where it is controlled.

And of course left entirely up in the air is the question of reference
signals: the bias imposed by some other system on the sensing of the
controlled variable. The question of a hierarchy of control immediately
raises itself. All the organisms we study today are highly evolved,
three and a half billion years' worth. It would probably be impossible
to find any cellular organism in which a hierarchy of control has not
developed, even through the physical organism whose traces appear in the
fossil record seem not to have changed at all for hundreds of millions
of years. We can only conjecture about the source of reference signals
for these gene-regulators at a time when there were no higher levels of
organization.

Finally, the evidence that McClintock gathered, clear as it was, still
only pertained to visible concomitants of whatever these gene-control

systems are really controlling. What we use as markers of genetic
identity are, must be, only side-effects of controlling the variables
that are really under control. Whether a kernel of maize presents a
colorless appearance, a solid pattern of darker color, a scattering of
spots, or a combination of colors and spots, is only what strikes the
eye of the human observer. This may have some peripheral bearing on
natural selection, but the central question is what hidden
characteristics that matter to the maize go along with these externally
visible side-effects. As always in thinking about PCT, we must ask
what's in it for the organism. Perhaps the only significance is in the
external appearance, as in the case of eye-spots on the wings of moths.
But we must also always consider whether we aren't observing something
of no significance to the organism itself, like fingerprints or eye
color, that merely follows upon controlling some other physiological
variable in a particular state.

There is, most fortunately for all of us, a cell biologist listening in
who not only knew Barbara McClintock and considered himself her friend,
but who is determined to continue the work of understanding cellular
systems -- and to do so using the principles of PCT. So there is some
justice in the world to allay my seething vicarious outrage at the
treatment this genius of a woman received.

On the other hand, I heard a quotation the other day: "If there's any
justice in the world, I'm in deep trouble."
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Best to all,

Bill P.