
New York Times February 19, 2001
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."
** NOTICE: In accordance with Title 17 U.S.C. Section 107, this material is distributed for research and educational purposes only. **
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