366
Z. RYCHTER
3rd to the 5th day of incubation. His interpretation is based on the
study of mitotic activity (expressed as mitotic index) of various parts of
the heart loop. The mitotic index alone, however, does not reliably
indicate high proliferation and metabolic rates, because the mitotic
index does not reveal the mitotic duration, which could be different in
various regions of the heart loop according to the degree of maturity of
the cell groups concerned (Lemez and Rychter, 1958; Jelinek, 1959).
Rychter and Lemez (1959b, 1960b), on the contrary, evoked transposition of the aorta between 2 days 12 hr and 3 days 18 hr of incubation. By a combination of experimental interventions (Section IV, A) it
has been possible, however, to shift the upper limit of the critical period
(i.e., the 'termination period' of Schwalbe, 1906) up to 4 days 8 hr.
Naturally, it is impossible to go beyond the latest stage in which the
heart bulb occupies such a position that the stopping of its morphogenetic movement can bring about the transposition of the aorta. On the
other hand, the authors believe that the earlier limit of the critical
period can be extended to the time of the genetic determination, i.e., to
fertilization, provided a suitable experimental technique is devised.
I t has long been known that the critical period can be extended by
use of noxious agents in high doses (e.g., Job et aL, 1935; Warkany and
Schraffenberger, 1947; Haskin, 1948). That the same effect can be
attained by a combination of two different experimental interventions
with no direct relation to the malformation concerned, was recorded for
the first time by Rychter and Lemez (1959b, 1960b).
From the above it seems that Stockard's (1921) original conception of
the critical period ('critical moment'), based on susceptibility of the
quickly growing organ primordium only, requires revision. The paper of
Russell and Russell (1954) lends support to this. The authors emphasize
that 'usage of the term "critical period" does not imply that the immediate primordium of the character malformed as a result of irradiation at a
certain stage was damaged at that stage, that is, during the critical
period. It indicates merely, that the initial disturbance (in this case
ionizations) that touches off a chain of processes, regardless of their
complexity, must occur at a certain stage to give a certain end result'.
Gruenwald (1958) is convinced that 'the time at which development
begins to deviate from normal is the latest time that the given abnormality could have been provoked, although provocation may have
occurred at any time previously'. This fully agrees with the reviewer's
opinion. The critical period was recently discussed at a Ciba Foundation
Symposium on Congenital Malformations (1960), at which Warkany
emphasized that 'it is wrong to assume (without additional proof) that
most congenital malformations are due to "acute" adverse environmental interference at the time of their "critical periods" and to
Z. RYCHTER
3rd to the 5th day of incubation. His interpretation is based on the
study of mitotic activity (expressed as mitotic index) of various parts of
the heart loop. The mitotic index alone, however, does not reliably
indicate high proliferation and metabolic rates, because the mitotic
index does not reveal the mitotic duration, which could be different in
various regions of the heart loop according to the degree of maturity of
the cell groups concerned (Lemez and Rychter, 1958; Jelinek, 1959).
Rychter and Lemez (1959b, 1960b), on the contrary, evoked transposition of the aorta between 2 days 12 hr and 3 days 18 hr of incubation. By a combination of experimental interventions (Section IV, A) it
has been possible, however, to shift the upper limit of the critical period
(i.e., the 'termination period' of Schwalbe, 1906) up to 4 days 8 hr.
Naturally, it is impossible to go beyond the latest stage in which the
heart bulb occupies such a position that the stopping of its morphogenetic movement can bring about the transposition of the aorta. On the
other hand, the authors believe that the earlier limit of the critical
period can be extended to the time of the genetic determination, i.e., to
fertilization, provided a suitable experimental technique is devised.
I t has long been known that the critical period can be extended by
use of noxious agents in high doses (e.g., Job et aL, 1935; Warkany and
Schraffenberger, 1947; Haskin, 1948). That the same effect can be
attained by a combination of two different experimental interventions
with no direct relation to the malformation concerned, was recorded for
the first time by Rychter and Lemez (1959b, 1960b).
From the above it seems that Stockard's (1921) original conception of
the critical period ('critical moment'), based on susceptibility of the
quickly growing organ primordium only, requires revision. The paper of
Russell and Russell (1954) lends support to this. The authors emphasize
that 'usage of the term "critical period" does not imply that the immediate primordium of the character malformed as a result of irradiation at a
certain stage was damaged at that stage, that is, during the critical
period. It indicates merely, that the initial disturbance (in this case
ionizations) that touches off a chain of processes, regardless of their
complexity, must occur at a certain stage to give a certain end result'.
Gruenwald (1958) is convinced that 'the time at which development
begins to deviate from normal is the latest time that the given abnormality could have been provoked, although provocation may have
occurred at any time previously'. This fully agrees with the reviewer's
opinion. The critical period was recently discussed at a Ciba Foundation
Symposium on Congenital Malformations (1960), at which Warkany
emphasized that 'it is wrong to assume (without additional proof) that
most congenital malformations are due to "acute" adverse environmental interference at the time of their "critical periods" and to