AUG 27, 2001
What Only the Embryo Knows
By STEPHEN JAY GOULD
homas Henry Huxley designated three men as the finest intellects of
19th century natural history: his dear friend Charles Darwin; his
most worthy opponent Georges Cuvier; and Karl Ernst von Baer, who
discovered the mammalian egg cell in 1827 and wrote the founding
treatise of modern embryology in 1828. Of these three, posterity has
largely forgotten von Baer, who suffered a severe mental breakdown in
the 1830's, but then recovered and moved to Russia (not uncommon for
a German-speaking Estonian national), where he enjoyed a
distinguished second university career, largely in anthropology and
lasting well into the 1870's.
In 1828, von Baer enunciated the central principle of embryological
development, later known as "von Baer's law" and now regarded as the
correct interpretation of Ernst Haeckel's famous (and erroneous)
claim that "ontogeny recapitulates phylogeny," or that the successive
forms of embryology repeat the adult stages of a lineage's evolution
- with the gill slits of an early human embryo representing an
ancestral fish and the later tail an ancestral reptile, for example.
By contrast, von Baer proposed a principle of progressive
specification and differentiation: One can first tell that an embryo
will become a vertebrate and not some sort of invertebrate, then a
mammal and not another kind of vertebrate, then a carnivore and not a
rodent or ruminant, then a dog and not a cat, and finally Buster the
Beagle and not another breed.
Von Baer summarized his principle in an epigram: "The development of
the organism is the history of growing individuality in every
respect." In other words, successive narrowing and determination of
parts as complexity coagulates. No turning back after the blueprint
becomes finalized from a broad mass of initial potential. For an
appropriate literary metaphor, think of Lot's wife or Omar Khayyam's
lines: "The moving finger writes; and having writ, moves on."
Von Baer's law epitomizes the central issue, unfortunately rarely
discussed and little understood, in our current debate over embryonic
stem cells. The very structure of material reality imposes a
principle of trade- offs in both nature and human affairs: One always
gives something in order to gain. In particular, we usually pay for
complexity by surrendering flexibility - and von Baer's law
encapsulates the embryological version of this structural generality.
In genetic terms that von Baer could not know, each cell of our body
contains a full set of genes. But embryological differentiation into
a specialized adult role - as a brain cell, liver cell or heart cell,
for example - leads to a "freezing" or "turning off" of most of this
potential apparatus, leaving active only those few components
regulating the specialized adult form and function. The cells of the
earliest, undifferentiated embryo (little more than a clump of
identical units in appearance) maintain full capacity to develop in
any direction; that is, all their genes remain potentially active and
recruitable.
The irony of the trade-off, explicitly recognized by von Baer nearly
200 years ago, inheres in the evolved surrender of this embryonic
flexibility as development proceeds toward our maximal complexity.
Cut a planarian flatworm in two, and the tail end regenerates a head
while the head end regrows a tail. For in this simplest of
bilaterally symmetrical invertebrates, with minimal differentiation
of internal organs, all cells retain the embryonic potential to build
any part of the body. This capacity for regeneration - the ability of
cells at a wound site to "dedifferentiate," or return to a state of
early embryonic flexibility - becomes progressively lost in animals
that evolve greater adult complexity by von Baer's universal process
of "locking in," with increasing specialization of parts. We have, in
short, traded regenerative capacity for the undeniable evolutionary
advantages of maximal complexity.
For this reason, we must use embryonic stem cells if we wish to
pursue a large body of enormously important, highly promising and
deeply humane research in how specific tissues and organs grow from
the broad potential of early cells derived from the fertilized ovum.
Speaking personally, I do not grant the status of a human life to a
clump of cells in a dish, produced by fertilization in vitro and
explicitly destined for discard by the free decision of the man and
woman who contributed the components. But I also have no desire to
offend the sensibilities of those who disagree. Thus, if I could
derive cells of similar flexibility in a different way, I would
gladly do so, even at considerable extra time and expense. (By
analogy, I did not mean to mock or flout our laws in using marijuana
to stave off severe and continuous nausea during some particularly
nasty and lengthy chemotherapy 20 years ago. But I tried all the
available anti- emetics, and they just didn't work. I continue to
regard my decision as fair, humane and, believe me, importantly
sustaining and life-affirming.)
Unfortunately, von Baer's law, and nature's broader structural rules
of trade-off between complexity and flexibility, give us no
alternative to embryonic stem cells for now - and the research is
important and far more than merely theoretically lifesaving.
(Moreover, if we hope to find ways to dedifferentiate adult cells -
and therefore learn to recover the requisite flexibility from cells
derived without offense to anyone - then we must experiment with
embryonic cells in order to understand and control the mechanism of
their broad potentiality).
As an old man, from his Russian periphery, von Baer made the famous
and rueful remark that all new and truly important ideas must pass
through three stages: first dismissed as nonsense, then rejected as
against religion, and finally acknowledged as true, with the proviso
from initial opponents that they knew it all along. Genetic
technology has brought us through the first stage. Our current debate
on stem cells resides in von Baer's second stage, with the religious
views of a clear, if powerful, minority setting an unfortunate
opposition to one of the most vital avenues of beneficial research in
our time. The third stage will arrive, and we will marvel that we
ever rejected a pathway toward knowledge so imbued with life-saving
capacity. May this third stage come soon, as our understanding
differentiates further into a true and humane grasp of the virtues of
flexibility.
Stephen Jay Gould, a professor of zoology at Harvard, is the author
of ``Questioning the Millennium.''
Copyright 2001 The New York Times Company
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