VI.
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295
differences in the haemoglobin molecule. Thus sickle cell haemoglobin
varies from normal haemoglobin by one amino residue (Ingram, 1957).
The synthesis of sickle cell haemoglobin in cellular particulate extracts
from normal haemoglobin-producing cells would lead to the inference
that external metabolite ratios could cue alterations in initial genecontrolled synthetic processes. A direct analytical result of this experiment is presently improbable and the answer must be sought by indirect
means. The synthesis of host specific melanins in grafted donor melanoblasts is also subject to test.
Evidence has been published to the effect that in the production of
antibody, only one or at the most two antibodies are produced by a
single cell. The inference is clear from such analyses that only one
genetic locus need be involved in directing the single cell's response to
an external agent (antigen). The production of two antibodies from two
external agents can be interpreted as the expression of allelic pairs in a
heterozygous cell (Nossal and Lederberg, 1958). The fact that any
population of antibody-producing cells may produce a large number of
reactive globulins has been postulated (Lederberg, 1959) to be due to a
randomization of certain base pairing mechanisms at the chromosomal
site for globulin synthesis. To postulate a multitude of such sites for
each globulin synthesized would require far too many sites in any
possible DNA polymer and concepts of preadaptability to the most
bizarre and artificial antigenic stimuli. However, the formulation by
Lederberg opens the way to understanding the means whereby external
stimuli can mould the overt manifestations of gene initiated syntheses.
Whether such a scheme can account for the manifold processes of
cellular differentiations has yet to be ascertained. It can, however, lead
to a discussion of the possible primacy of external metabolic cues as the
initiator of differentiative processes.
Evidence has been presented earlier in this review concerning experiments in which externally supplied low molecular weight compounds
act as apparent initiators of processes leading to overt differentiations.
These effects have been sufficiently powerful to overcome previously
ordered synthetic pathways and divert the cellular machinery to
syntheses of a different specific character. These data can be interpreted
by means of concepts of adaptive enzyme formation. Another closely
related interpretation is that several synthetic pathways are open to the
cell at any one time. The alteration of the environmental ratios of
metabolites serves to foster one reaction series by increased substrate
availability, while another is limited by differences in reaction rate or
by limitation of the competing alternative reaction series. There is little
evidence available at the moment to enable a choice to be made between
these alternatives. However, both of the schemes make possible (but
DIFFERENTIATION OF VERTEBRATE PIGMENT CELLS
295
differences in the haemoglobin molecule. Thus sickle cell haemoglobin
varies from normal haemoglobin by one amino residue (Ingram, 1957).
The synthesis of sickle cell haemoglobin in cellular particulate extracts
from normal haemoglobin-producing cells would lead to the inference
that external metabolite ratios could cue alterations in initial genecontrolled synthetic processes. A direct analytical result of this experiment is presently improbable and the answer must be sought by indirect
means. The synthesis of host specific melanins in grafted donor melanoblasts is also subject to test.
Evidence has been published to the effect that in the production of
antibody, only one or at the most two antibodies are produced by a
single cell. The inference is clear from such analyses that only one
genetic locus need be involved in directing the single cell's response to
an external agent (antigen). The production of two antibodies from two
external agents can be interpreted as the expression of allelic pairs in a
heterozygous cell (Nossal and Lederberg, 1958). The fact that any
population of antibody-producing cells may produce a large number of
reactive globulins has been postulated (Lederberg, 1959) to be due to a
randomization of certain base pairing mechanisms at the chromosomal
site for globulin synthesis. To postulate a multitude of such sites for
each globulin synthesized would require far too many sites in any
possible DNA polymer and concepts of preadaptability to the most
bizarre and artificial antigenic stimuli. However, the formulation by
Lederberg opens the way to understanding the means whereby external
stimuli can mould the overt manifestations of gene initiated syntheses.
Whether such a scheme can account for the manifold processes of
cellular differentiations has yet to be ascertained. It can, however, lead
to a discussion of the possible primacy of external metabolic cues as the
initiator of differentiative processes.
Evidence has been presented earlier in this review concerning experiments in which externally supplied low molecular weight compounds
act as apparent initiators of processes leading to overt differentiations.
These effects have been sufficiently powerful to overcome previously
ordered synthetic pathways and divert the cellular machinery to
syntheses of a different specific character. These data can be interpreted
by means of concepts of adaptive enzyme formation. Another closely
related interpretation is that several synthetic pathways are open to the
cell at any one time. The alteration of the environmental ratios of
metabolites serves to foster one reaction series by increased substrate
availability, while another is limited by differences in reaction rate or
by limitation of the competing alternative reaction series. There is little
evidence available at the moment to enable a choice to be made between
these alternatives. However, both of the schemes make possible (but