The Questions of Developmental Biology

Chains of causation
Whether in law or science, establishing chains of
causation is a demanding and necessary task.
In developmental toxicology, numerous endpoints must be
checked, and many different levels of causation have to be
established (Crain and Guillette 1998; McNabb et al.
1999). For instance, one could ask if the pollutant spill in
Lake Apopka was responsible for the feminization of male
alligators. To establish this, one has to ask how might the
chemicals in the spill contributed to reproductive anomalies
in males alligators and what would be the consequences of
that happening. Table 21.3 shows the postulated chain of
causation. After observing that the population level of the alligators has declined, at the organism
level one discovers the unusually high levels of estrogens in the female alligators, the unusually
low levels of testosterone in the males, and the decrease in the number of births among the
alligators. On the tissue and organ level, the decline in birth rate can be explained by the elevated
production of estrogens from the juvenile testes, the malformation of the testes and penis, and the
changes in enzyme activity in the female gonads. On the cellular level, one sees ovarian
abnormalities that correlate with unusually elevated estrogen levels. These cellular changes, in
turn, can be explained at the molecular level by the finding that many of the components of the
pollutant spill bind to the alligator estrogen and progesterone receptors and that they are able to
circumvent the cell's usual defenses against overproduction of steroid hormones (Crain et al.
1998).
While there is little dispute about the damage to wildlife being wrought by endocrine
disrupting chemicals, it is difficult to document the effects of environmental compounds on
humans. There is enormous genetic variation in the human species, and one cannot perform
controlled experiments to determine the effect of any particular compound on a human
population. Rather, we are exposed to "cocktails" consisting of different compounds ingested at
different times.
Table 21.3. Chain of causation linking contaminant spill in Lake
Apopka to endocrine disruption in juvenile alligators
Level
Population
Organism
Evidence
The juvenile alligator population in Lake Apopka has
decreased.
Juvenile Apopka females have elevated circulating levels
of estradiol-17 β.
Juvenile Apopka males have depressed circulating
concentrations of testosterone.