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The proposition that the creations of art are unique (in the sense tbat we would not have had Timon of Athenshad Shakespeare not lived), whereas the creations of science are inevitable or commonplace (in the sense that we would have had the DNA double helix even if Watson and Crick had not lived), has little philosophical or historical merit. For, this proposition conflates works of art and science (the texts of the play Timonand of the paper A structure for Deoxyribose Nucleic Acid), both of which are unique, and their semantic content (the insights into human affects provided by Timonand the concept of the DNA double helix), both of which are commonplace as well as unique.

The salivary glands of the blood-sucking leech Haementeria ghilianiicontain an anticoagulant that not only inhibits the clotting of human and bovine plasma, but also dissolves previously formed fibrin clots. This anticoagulant activity is attributable to an enzyme, for which the name hementin is proposed. Hementin catalyzes the proteolytic degradation of fibrinogen and fibrin, even in the presence of the inhibitors of proteases occurring in human plasma. The enzyme has the same affinity for human fibrinogen and fibrin. In human fibrinogen cleaves the Act chain initially and then the γ chain to yield characteristic fragments of high molecular weight that are different from the fragments resulting from the digestion of fibrinogen by plasmin. The salivary extracts do not contain any appreciable amounts of an activator of human plasminogen or an inhibitor of human or bovine thrombin. Thus, H. ghilianiiprevents coagulation of its host blood through a fibrinogenolytic mechanism that is entirely different from that of hirudin, a thrombin-inactivating polypeptide present in the saliva of another leech, Hirudo medicinalis.

A network of intra- and intersegmental synaptic connexions has been identified in the ventral nerve cord of the leech that links the set of oscillatory interneurones of the central swim oscillator to the motor neurones commanding the swimming rhythm. Excitatory connexions lead from oscillatory interneurones to both excitatory and inhibitory motor neurones, whereas inhibitory connexions lead from oscillatory interneurones to only the inhibitory motor neurones. Connexions leading from a motor neurone back to the oscillatory interneurones were found in only one exceptional case, an inhibitory motor neurone previously known to have access to the central swim oscillator. This network of identified connexions can account reasonably well for the mechanism by which the oscillatory interneurones drive their follower motor neurones into the phasic activity pattern characteristic of the swimming movement.

Four oscillatory interneurones that appear to be the principal components of the central swim oscillator of Hirudo medicinalis have been identified on each side of the segmental ganglia of the ventral nerve cord. During ‘swimming’ episodes of an isolated nerve cord preparation each interneurone undergoes a polarization rhythm that is phase-locked with the impulse burst rhythm of the motor neurones known to drive the swimming movement. Passage of current into any of the interneurones can shift the phase of the swim rhythm. One of the interneurones projects its axon rearward to posterior ganglia and the other three project their axons frontward to anterior ganglia. The oscillatory interneurones are connected both intra- and interganglionically to form a topologically complex intersegmental network of concatenated ring circuits that possess the feature of recurrent cyclic inhibition. Theoretical analysis and electronic analogue models show that the network is inherently oscillatory and can produce both a cycle period and intra- and intersegmental phase relations of its elements that are appropriate for generating the body wave of the swimming movement.

Segmentation in the leech embryo is established by a stereotyped cell lineage. Each of the 32 segments arises from homologous, bilaterally symmetrical complements of mesodermal and ectodermal blast cell clones. Although segments are homologous, they are regionally differentiated along the longitudinal body axis. Various segments display idiosyncratic ensembles of features, which constitute discrete segmental identities. The differentiation of segment-specific features, such as the mesoderm-derived nephridia, genital primordia and identified Small Cardioactive Peptide immunoreactive neurons, reflects a diversification of the developmental fates of homologous blast cell clones. We have investigated whether segment-specific differentiation of homologous mesodermal blast cell clones depends on cellintrinsic mechanisms (based on the cells’ lineage history) or on cell-extrinsic mechanisms (based on the cells’ interactions with their environment) in embryos of Theromyzon rude. For this purpose, we first mapped the segment-specific fates of individual mesodermal blast cell clones, and then induced mesodermal clones to take part in the formation of segments for which they are not normally destined. Two types of ectopic segmental position were produced: one in which a mesodermal blast cell clone was out of register with all other consegmental cells and one in which a mesodermal blast cell clone was out of register with its overlying ectoderm, but was in normal register with the mesoderm and ectoderm on the other side of the embryo. Mesodermal blast cell clones that developed in either type of ectopic segmental position gave rise to segment-specific features characteristic of their original segmental fates rather than their ectopic positions. Thus, the development of segmental identity in the leech mesoderm is attributable to a cell-intrinsic mechanism and, either before or soon after their birth, mesodermal blast cells are autonomously committed to segment-specific fates.

The germinal plate of 5- to 12-day-old embryos of the leech Hirudo medicinalis consists of an anterior and a posterior sector that differ both structurally and developmentally. The posterior sector includes the five pairs of teloblasts and five paired longitudinal bandlets of stem cells and their descendant blast cells. The mesoteloblast pair and their descendant cells of the m bandlet divide spirally and give rise to bilaterally paired cell clusters. The four ectoteloblast pairs and their descendant cells of the n, o, p and q bandlet pairs divide unidirectionally and give rise to paired one-cell-thick and four-cell-wide ectodermal arches. The developmentally more advanced anterior sector of the germinal plate consists of differentiating ectodermal and mesodermal cells engaged in organogenesis. The mesodermal cell clusters develop into somites, whereas the expanding ectodermal arches develop into nerve cord ganglia and epidermis. Rostrocaudal expansion of somite tissue results in the formation of obliquely oriented intersegmental septa, causing the ganglia to take on an intersegmental distribution. The first sign that formation of body segments has been completed is the appearance of a bilateral gap in the mesodermal bandlet of the posterior sector of the germinal plate. This gap seems to trigger degeneration of the posterior sector of the germinal plate.

The inactivation of the phages T1, T2, T3, T5, T7, and λ by decay of incorporated P32 has been studied. It was found that these phages fall into two classes of sensitivity to P32 decay: at the same specific activity of P32 in their deoxyribonucleic acid (DNA), T2 and T5 are inactivated three times as rapidly as T1, T3, T7, and λ. Since the strains of the first class were found to contain about three times as much total phosphorus per phage particle as those of the second) it appears that the fraction of all P32 disintegrations which are lethal is very nearly the same in all the strains. This fraction α depends on the temperature at which decay is allowed to proceed, being 0.05 at –196°C., 0.1 at +4°C., and 0.3 at 65°C. Decay of P32 taking place only after the penetration of the DNA of a radioactive phage particle into the interior of the bacterial cell can still prevent the reproduction of the parental phage, albeit inactivation now proceeds at a slightly reduced rate. T2 phages inactivated by decay of P32 can be cross-reactivated; i.e., donate some of their genetic characters to the progeny of a mixed infection with a non-radioactive phage. They do not, however, exhibit any multiplicity reactivation or photoreactivation. The fact that at low temperatures less than one-tenth of the P32 disintegrations are lethal to the phage particle and the dependence of the fraction of lethal disintegrations on temperature can be accounted for by the double stranded structure of the DNA macromolecule.

Cultures of Escherichia coli will not grow in media containing very high specific activities of radiophosphorus P32, the inhibition of growth being due to the decay of assimilated P32 atoms. Experiments with a differentially labeled thymineless strain of E. coli show that the P32 disintegrations which occur in the bacterial deoxyribonucleic acid, i.e. in the nucleus, are mainly responsible for the inactivation of the cell. The kinetics with which radioactive bacterial populations are inactivated indicate that the function of several nuclei per bacterial cell must be eliminated by P32 decay before the ability to generate a colony is lost. The efficiency with which each P32 disintegration inactivates the nucleus in which it has occurred is calculated to be 0.02 (at –196°), i.e., similar in magnitude to the killing efficiency of P32 decay in bacteriophages. P32 decay and thymine starvation cooperate in bringing about the death of individuals of the thymineless strain, from which observation it is inferred that "thymineless death" is likewise a nuclear inactivation. The descendants of a non-radioactive bacterial culture grown for several generations in the presence of P32 and the descendants of a radioactive culture grown in the absence of P32 are inactivated by P32 decay in a manner which indicates that the phosphorus atoms of bacterial nuclei are dispersed among the progeny nuclei in their line of descendance.

The multiplication of vegetative T2 bacteriophage in B/r bacteria has been followed by studying the lethal effects of decay of incorporated radiophosphorus P32 at various stages of the eclipse period. Experiment I. Non-radioactive B/r bacteria were infected with highly radioactive (i.e. P32-unstable) T2 and infection allowed to proceed at 37°C. for various numbers of minutes before freezing the infected cells and storing them in liquid nitrogen. The longer development had been allowed to proceed at 37°C. before freezing, the slower the inactivation of the frozen infective centers by P32 decay. Samples which were frozen after incubation for 9 minutes were completely stable. Experiment II. Radioactive B/r bacteria in radioactive growth medium were infected with non-radioactive (i.e. stable) T2 and incubated for various lengths of time before being frozen and stored in liquid nitrogen, like those of Experiment I. In this case, the infective centers were stable to P32 decay as long as they were frozen before the end of the eclipse period. The T2 progeny phages issuing from the infected bacteria were P32-unstable. Experiment III. Radioactive B/r bacteria in radioactive medium were infected with radioactive (i.e. P32-unstable) T2 and otherwise incubated and frozen like those of the first two experiments. In this case, the same progressive stabilization, of the infective centers towards inactivation by P32 decay was observed as that found in Experiment I. The ability to yield infective progeny of infected bacteria incubated for 10 minutes at 37°C. before freezing could no longer be destroyed by P32 decay. The progeny issuing from the infected cells were as unstable as the parental phage. These results could be explained by one of three general hypotheses. As vegetative phage begins to multiply, it is possible that: (a) there is a high probability that any part of the vegetative phage already duplicated can be saved after its destruction by P32 decay through a process analogous to multiplicity reactivation or, (b) there occurs a change in state of the deoxyribonucleic acid (DNA) preliminary to or in the course of its replication that renders it refractory to destruction by P32 decay, or, finally (c) there occurs a transfer of the genetic factors from the DNA of the infecting phage to another substance not sensitive to destruction by P32 decay.

A response by Gunther S. Stent to two letters to the editor about his article "Prematurity and Uniqueness in Scientific Discovery" in the December 1972 issue is presented.