The Questions of Developmental Biology

absent (Figure 1.16A). Over 7000 affected infants were born to women who took this drug, and a
woman need only have taken one tablet to produce children with all four limbs deformed (Lenz
1962, 1966; Toms 1962). Other abnormalities induced by the ingestion of thalidomide included
heart defects, absence of the external ears, and malformed intestines.
Nowack (1965) documented the period of susceptibility during which thalidomide caused
these abnormalities. The drug was found to be teratogenic only during days 34 50 after the last
menstruation (about 20 to 36 days postconception). The specificity of thalidomide action is
shown in Figure 1.16B. From day 34 to day 38, no limb abnormalities are seen. During this
period, thalidomide can cause the absence or deficiency of ear components. Malformations of
upper limbs are seen before those of the lower limbs, since the arms form slightly before the legs
during development. The only animal models for thalidomide, however, are primates, and we still
do not know the mechanisms by which thalidomide causes human developmental disruptions.
Thalidomide was withdrawn from the market in November 1961, but it is beginning to be
prescribed again, this time as a potential anti-tumor and anti-autoimmunity drug (Raje and
Anderson 1999).
The integration of anatomical information about congenital malformations with our new
knowledge concerning the genes responsible for development has had a revolutionary effect and
is currently restructuring medicine. This integration is allowing us to discover the genes
responsible for inherited malformations, and it permits us to identify the steps in development
being disrupted by teratogens. We will see examples of this integration throughout this text, and
Chapter 21 will detail some of the remarkable new discoveries in teratology.
*The word "monster," used frequently in textbooks prior to the mid-twentieth century to describe
malformed infants, comes from the Latin monstrare, "to show or point out." This is also the root
of our word "demonstrate." It was realized by Meckel (of jaw cartilage fame) that syndromes of
congenital anomalies demonstrated certain principles about normal development. Parts of the
body that were affected together must have some common developmental origin or mechanism
that was being affected.
Mathematical Modeling of Development
Developmental biology has been described as the last refuge of the mathematically
incompetent scientist. This phenomenon, however, is not going to last. While most embryologists
have been content trying to analyze specific instances of development or even formulating some
general principles of embryology, some researchers are now seeking the laws of development.
The goal of these investigators is to base embryology on formal mathematical or physical
principles (see Held 1992; Webster and Goodwin 1996). Pattern formation and growth are two
areas in which such mathematical modeling has given biologists interesting insights into some
underlying laws of animal development.