311gradually revealed itself as the embryo grew in size and emerged from the yolk (Roe
1975 ). von Haller found evidence supporting his view in the earliest microscopic
studies of developing vertebrates and invertebrates by Malpighi and Swammerdam,
respectively. Malpighi and Swammerdam both observed embryonic versions of
adult organs in their studies, but neither explicitly endorsed a theory of preformation
(Cobb 2000 ). von Haller also examined chicken embryos himself, and found further
support for his views on preformation. For example, he claimed that the membranes
of the yolk sac were continuous with those of the intestine. Since the yolk mem-
brane was clearly present in the unfertilized embryo, he concluded the intestinal
membrane must also be present (Haller and Arnay 1758 ; Roe 1975 ). From this and
other work, von Haller deduced the existence of an invisible embryo in untreated
unfertilized eggs, complete with preformed versions of adult organs. Embryonic
development was merely the process of organs growing in size after fertilization,
becoming more opaque and visible to the eye over time. To explain why the differ-
ent organs became visible at different times, he suggested that different parts of the
embryo grow at different rates. He predicted that more powerful microscopes would
eventually reveal the elusive preformed embryo (Keezer 1965 ).
Caspar Friedrich Wolff was a contemporary of von Haller’s and a leading propo-
nent of the theory of epigenesis (Roe 1981 ). The concept of epigenesis was origi-
nally formulated by Aristotle and held that organs and tissues are formed de novo
with each generation (Aristotle and Peck 1943 ). Epigenesis was discredited in the
Middle Ages along with Aristotelian physics, but was revived in a different form by
William Harvey (1578–1657) in his 1651 treatise Exercitationes de generatione
animalium (Harvey 1651 ). Harvey’s epigenetic theory was not based on direct
observation of development, since he never observed an egg or embryo under a
microscope (Keezer 1965 ). The first experimental evidence supporting epigenesis
came only in 1742, when Abraham Trembley (1710–1784) discovered the ability of
freshwater polyps to regenerate after being cut in half (Roe 1975 ). This showed that
some animals could regenerate structures de novo, but left open the question of how
the animal was generated in the first place. To answer this question, Wolff per-
formed a careful microscopic examination of early chicken embryos. He found that
organs are generated through a process involving the folding of embryonic mem-
branes in a precise and reproducible manner (Meyer 1932 ; Roe 1975 ). This folding
could not be explained if embryonic development was merely the result of changes
in size or opacity of preexisting organs. But Wolff did not fully appreciate the sig-
nificance of the embryonic membranes. He thought they were an inorganic covering
that moved passively in response to external forces (Schmitt 2005 ). Like all previ-
ous proponents of epigenesis, Wolff invoked the action of a mystical “vital force” to
shape the embryo. To von Haller, this was the fatal flaw of epigenesis. He wrote that
epigenesis invoked, “... a force that seeks, that chooses, that has a purpose, that
against the laws of blind combination always and infallibly casts the same throw ...
I do not find in all nature the force that would be sufficiently wise to join together
the single parts of the millions and millions of vessels, nerves, fibers and bones of a
body according to an eternal plan ...” (Roe 1981 ). Thus, epigenesis failed because
no one could provide a satisfactory mechanism.
7 Establishment of the Vertebrate Germ Layers