S J Gould on new genome findings

Aside from the fact that this op/ed piece addresses the subject matter of
many past fights on this list, its significance for epistemology and the
sociology of knowledge (and hence, world-systems theory) should be
obvious.  I especially like the line about Parsifal and the reference to
the Abe Lincoln inaugural address.

--


February 19, 2001




Humbled by the Genome's Mysteries


By STEPHEN JAY GOULD

Two groups of researchers released the formal report of data for the human
genome last Monday — on the birthday of Charles Darwin, who jump-started our
biological understanding of life's nature and evolution when he published
"The Origin of Species" in 1859. On Tuesday, and for only the second time in
35 years of teaching, I dropped my intended schedule — to discuss the
importance of this work with my undergraduate course on the history of life.
(The only other case, in a distant age of the late 60's, fell a half-hour
after radical students had seized University Hall and physically ejected the
deans; this time at least, I told my students, the reason for the change lay
squarely within the subject matter of the course!)
I am no lover, or master, of sound bites or epitomes, but I began by telling
my students that we were sharing a great day in the history of science and
of human understanding in general.

The fruit fly Drosophila, the staple of laboratory genetics, possesses
between 13,000 and 14,000 genes. The roundworm C. elegans, the staple of
laboratory studies in development, contains only 959 cells, looks like a
tiny formless squib with virtually no complex anatomy beyond its genitalia,
and possesses just over 19,000 genes.
The general estimate for Homo sapiens — sufficiently large to account for
the vastly greater complexity of humans under conventional views — had stood
at well over 100,000, with a more precise figure of 142,634 widely
advertised and considered well within the range of reasonable expectation.
Homo sapiens possesses between 30,000 and 40,000 genes, with the final tally
almost sure to lie nearer the lower figure. In other words, our bodies
develop under the directing influence of only half again as many genes as
the tiny roundworm needs to manufacture its utter, if elegant, outward
simplicity.

Human complexity cannot be generated by 30,000 genes under the old view of
life embodied in what geneticists literally called (admittedly with a sense
of whimsy) their "central dogma": DNA makes RNA makes protein — in other
words, one direction of causal flow from code to message to assembly of
substance, with one item of code (a gene) ultimately making one item of
substance (a protein), and the congeries of proteins making a body. Those
142,000 messages no doubt exist, as they must to build our bodies'
complexity, with our previous error now exposed as the assumption that each
message came from a distinct gene.
We may envision several kinds of solutions for generating many times more
messages (and proteins) than genes, and future research will target this
issue. In the most reasonable and widely discussed mechanism, a single gene
can make several messages because genes of multicellular organisms are not
discrete strings, but composed of coding segments (exons) separated by
noncoding regions (introns). The resulting signal that eventually assembles
the protein consists only of exons spliced together after elimination of
introns. If some exons are omitted, or if the order of splicing changes,
then several distinct messages can be generated by each gene.

The implications of this finding cascade across several realms. The
commercial effects will be obvious, as so much biotechnology, including the
rush to patent genes, has assumed the old view that "fixing" an aberrant
gene would cure a specific human ailment. The social meaning may finally
liberate us from the simplistic and harmful idea, false for many other
reasons as well, that each aspect of our being, either physical or
behavioral, may be ascribed to the action of a particular gene "for" the
trait in question.
But the deepest ramifications will be scientific or philosophical in the
largest sense. From its late 17th century inception in modern form, science
has strongly privileged the reductionist mode of thought that breaks overt
complexity into constituent parts and then tries to explain the totality by
the properties of these parts and simple interactions fully predictable from
the parts. ("Analysis" literally means to dissolve into basic parts). The
reductionist method works triumphantly for simple systems — predicting
eclipses or the motion of planets (but not the histories of their complex
surfaces), for example. But once again — and when will we ever learn? — we
fell victim to hubris, as we imagined that, in discovering how to unlock
some systems, we had found the key for the conquest of all natural
phenomena. Will Parsifal ever learn that only humility (and a plurality of
strategies for explanation) can locate the Holy Grail?
The collapse of the doctrine of one gene for one protein, and one direction
of causal flow from basic codes to elaborate totality, marks the failure of
reductionism for the complex system that we call biology — and for two major
reasons.

First, the key to complexity is not more genes, but more combinations and
interactions generated by fewer units of code — and many of these
interactions (as emergent properties, to use the technical jargon) must be
explained at the level of their appearance, for they cannot be predicted
from the separate underlying parts alone. So organisms must be explained as
organisms, and not as a summation of genes.
Second, the unique contingencies of history, not the laws of physics, set
many properties of complex biological systems. Our 30,000 genes make up only
1 percent or so of our total genome. The rest — including bacterial
immigrants and other pieces that can replicate and move — originate more as
accidents of history than as predictable necessities of physical laws.
Moreover, these noncoding regions, disrespectfully called "junk DNA," also
build a pool of potential for future use that, more than any other factor,
may establish any lineage's capacity for further evolutionary increase in
complexity.

The deflation of hubris is blessedly positive, not cynically disabling. The
failure of reductionism doesn't mark the failure of science, but only the
replacement of an ultimately unworkable set of assumptions by more
appropriate styles of explanation that study complexity at its own level and
respect the influences of unique histories. Yes, the task will be much
harder than reductionistic science imagined. But our 30,000 genes — in the
glorious ramifications of their irreducible interactions — have made us
sufficiently complex and at least potentially adequate for the task ahead.
 

We may best succeed in this effort if we can heed some memorable words
spoken by that other great historical figure born on Feb. 12 — on the very
same day as Darwin, in 1809. Abraham Lincoln, in his first Inaugural
Address, urged us to heal division and seek unity by marshaling the "better
angels of our nature" — yet another irreducible and emergent property of our
historically unique mentality, but inherent and invokable all the same, even
though not resident within, say, gene 26 on chromosome number 12.

Stephen Jay Gould, a professor of zoology at Harvard, is the author of
"Questioning the Millennium."





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