COMMENTARY ON ZOHAR'S “PROSPECTS FOR‘GENETIC THERAPY’- CAN A PERSON BENEFIT FROM BEING ALTERED?”

In his paper on the effects of Prenatal Genetic Intervention (PGI) on personal identity, Noam Zohar comes to a conclusion about genetic makeup and the uses of gene therapy quite different from the one I reach in another piece in this issue. Zohar's argument rests on the contention that personal identity changes with alteration of the genome, following what I have identified as the "constitutive" view. To see that this is the pillar supporting the weight of his argument, consider the following. Questions of identity aside, how can it be that altering the genome of children suffering from Lesch-Nyhan syndrome or Tay-Sachs disease so that they now produce the enzyme that they formerly lacked does not benefit them? Clearly, if their identities were not changed, such individuals would in fact realize great benefit from PGI, since the devastating bad effects of the genetic flaw would be avoided. Such a change would certainly make the altered individuals better off, that is, it would benefit them. On this, Zohar and I do not disagree. Persistence of identity through such genetic change is the sticking point.     

Temporal variation in abundance of the egg predator Carcinonemertes epialti (Nemertea) and its effect on egg mortality of its host,the shore crab,Hemigrapsus oregonensis

An outbreak of the nemertean, Carcinonemertes epialti, was observed on Hemigrapsus oregonensis during October, 1982 at Campbell Cove, Bodega Harbor, California. Mean worm intensity (296 worms/crab) was the highest recorded for this nemertean egg predator on H. oregonensis. During the outbreak, male crabs were found to harbor more worms than both non-ovigerous and ovigerous females. Crab egg mortality was substantial; 83% of the ovigerous females experienced 75–100% brood mortality. The seasonal peak in worm abundance coincided with the seasonal low in crab reproduction at this locality. A method for estimating the impact of C. epialti on H. oregonensis natality was developed using crab size and fecundity, and worm prevalence and intensity. For a non-outbreak sampling period, a mean of 5.6% egg mortality was experienced by infested crabs for the period selected. Thus, brood mortality during the outbreak was much greater than that experienced at non-outbreak periods. Heavy fishing pressure on some commercially important crab species has been suggested as a possible factor inducing worm outbreaks and facilitating their continued persistence. These observations suggest that fisheries are not necessarily responsible for the outbreaks of nemerteans on commercially important crab species. However, fishing pressure may still be a sufficient condition to promote nemertean outbreaks.     

Formation of the transverse nerve in moth embryos : I. A scaffold of nonneuronal cells prefigures the nerve

We have studied the embryonic development of the transverse nerve (TN), an unpaired segmental nerve of the moth Manduca sexta. Two identified motor neurons and 16 identified neuroendocrine neurons project axons within the larval TN; therefore, the TN is both a peripheral nerve and a neurohaemal organ. At 33% of embryogenesis, and prior to the arrival of any neuronal growth cones, the position, shape, and trajectory of the TN are anticipated by two groups of nonneuronal cells that we call the strap and the bridge. At this time the strap and the bridge together consist of approximately 100 cells, all of which express a cell surface epitope recognized by the monoclonal antibody TN-1. As development proceeds, both the number of nonneuronal cells within the strap and the bridge and the fraction that expresses the TN-1 antigen(s) decrease. Moreover, individual cells within the strap become morphologically identifiable before the arrival of the neuronal growth cones. Most of the axons that project to the TN also express the TN-1 antigen(s) during their period of outgrowth. The two motor neuron growth cones are the first to reach the environment of the strap and the bridge, doing so at approximately 37%; having encountered these cellular structures, the growth cones restrict their navigation to this preexisting scaffolding, until they reach their muscle target. The neuroendocrine growth cones arrive later and also grow within the confines of the strap and the bridge (J.N. Carr and P.H. Taghert, 1988, Dev. Biol, 130, 500-512). In this first paper we describe the development of the strap and the bridge, and the interactions of the motor neuron growth cones with these structures. The observations are novel in documenting the extent and precision to which a peripheral nerve pathway is prefigured by a contiguous assemblage of nonneuronal cells.     

The determination of fresh organic carbon weight from formaldehyde preserved macrofaunal samples

Methodologies are presented whereby the fresh organic carbon weight of formaldehyde preserved macrofaunal samples may be estimated. Length-organic carbon weight regressions were determined for the four numerically dominant bivalves in Narragansett Bay, Rhode Island (Nucula annulata, Yoldia limatula, Mulinia lateralis, and Pandora gouldiana) and one commercially important, but less abundant species (Mercenaria mercenaria). Constants were determined to convert the dry weight of preserved softbodied organisms (polychaetes, oligochaetes, amphipods, etc.) to fresh (unpreserved) organic carbon weight. These results can be used by investigators studying the energetics of benthic communities similar to those in Narragansett Bay.     

Selective breeding for variations in patterns of mystacial vibrissae of mice. Bilaterally symmetrical strains derived from ICR stock

The establishment of certain patterns of mystacial vibrissae in mice has been the aim of an extensive breeding program carried on in this laboratory since 1977. In a companion paper we have reported on variations in this pattern in an outbred population of ICR mice. Starting with 21 ICR animals we bred, mostly by brother-sister mating, for 13 bilaterally symmetric patterns of mystacial vibrissae characterized by the presence (or absence) of supernumerary whiskers (SWs). The strains are classified as follows: I, a mouse strain with the standard pattern; II, eight strains bred for the occurrence of SWs at a given site or sites; and III, four mouse strains bred for a maximal number of SWs in different regions of the whiskerpad. Commonly, SWs occur in regions that coincide with the zones of mergence between the three facial processes except for two class II strains in which we bred for SWs in the "straddler" row of vibrissae, and for one class III strain, in which we cultivated the tendency (that appeared late in our program) to have SWs at the crest of a facial process. For classes I and II we analyzed the results for about 18 generations in terms of "improvement," meaning an increase in the percentages of animals with the desired phenotype together with a decreased frequency of undesired SWs. For class III, success in breeding meant the increase of the mean number of the desired SWs. All results led to the same conclusion: there is a genetic basis for the occurrence of SWs. The side preference of a particular SW is not strain dependent. It disappears in those class I and II strains in which almost 100% of animals obtained the desired phenotype. The increase in number of SWs in one zone of mergence does not depend on the presence of SWs in the other. Where tested, we almost always found a representation of an SW in a topologically equivalent location within the "barrelfield" area of the somatosensory cerebral cortex. Except for some diseases early in the breeding program, and some side effects of inbreeding that were eliminated, the population was without obvious defects. Where tested, there was no correlation between the occurrence of SWs and sex. The observed variations in pattern of mystacial vibrissae and their genetic background led us to propose a morphogenetic model for the formation of the pattern of mystacial vibrissae.     

Cloning and expression of a tylosin resistance gene from a tylosin-producing strain of Streptomyces fradiae

Summary A gene conferring high-level resistance to tylosin in Streptomyces lividans and Streptomyces griseofuscus was cloned from a tylosin-producing strain of Streptomyces fradiae. The tylosin-resistance (Tyl^r) gene (tlrA) was isolated on five overlapping DNA fragments which contained a common 2.6 Kb KpnI fragment. The KpnI fragment contained all of the information required for the expression of the Tyl^r phenotype in S. lividans and S. griseofuscus. Southern hybridization indicated that the sequence conferring tylosin resistance was present on the same 5 kb SalI fragment in genomic DNA from S. fradiae and several tylosin-sensitive (Tyl^s) mutants. The cloned tlrA gene failed to restore tylosin resistance in two Tyl^s mutants derived by protoplast formation and regeneration, and it restored partial resistance in a Tyl^s mutant obtained by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) mutagenesis. The tlrA gene conferred resistance to tylosin, carbomycin, niddamycin, vernamycin-B and, to some degree, lincomycin in S. griseofuscus, but it had no effect on sensitivity to streptomycin or spectinomycin, suggesting that the cloned gene is an MLS (macrolide, lincosamide, streptogramin-B)-resistance gene. Twenty-eight kb of S. fradiae DNA surrounding the tlrA gene was isolated from a genomic library in bacteriophage Charon 4. Introduction of these DNA sequence into S. fradiae mutants blocked at different steps in tylosin biosynthesis failed to restore tylosin production, suggesting that the cloned Tyl^r gene is not closely linked to tylosin biosynthetic genes.     

Distribution of Alginate Lyase Activity among Strains of Bacillus circulans

Strains from four different DNA relatedness groups of Bacillus circulans showed apparent alginate lyase activity; the activity of three strains examined had mannuronidase specificity. A representative strain of group 4 also produced apparent inducible unsulfated chrondroitin lyase activity.     

The social structure of primates

A comprehensive comparative study of the social structure of primates revealed: There is no social structure which can be considered typical and discriminative for primates. The varying social structures of the extant primate genera cannot be derived from each other: In contrast it seems that the basic, ancestral condition was that of solitary living animals, loosely aggregated. It can be assumed that the development to a gregarious society took place in two entirely different ways. In terms of primate phylogeny this different development can be shown for the prosimians as well as for the old world and new world monkeys as independently occurring processes. One way of behavioral specialization resulted in close pair bonds or in small family groups, whereas the other led to female groups. The presupposition for the forming of a society based on female groups is the close contact between the individuals and in addition to this, a remarkable social tolerance of females to each other. Social specializations which can be considered transitional from the basic condition are frequently found in prosimians. The kinds of social structures of the particular genera are in close relation to their taxonomic positions in the phylogenetic scala. The number of males in larger social groups of primates is substantially irrelevant as the groups are socially most dependent on the females. The protecting males are socially peripheral. The social units of most of the primate species are matrilocal and endure for several generations. In contrast, the social units of the gibbons and of the pongids are patrilocal and are established anew by the females in each generation. Consequently the social unit disintegrates on the death of the male. In all genera studied, male and female individuals present considerable behavioral differences which can be found even in juveniles. Primates are able to discriminate well known and confident individuals from other less confident; they prefer more confident individuals to less confident ones, and less confident to non-confident. As a consequence of this discriminative ability there is a clear preference for near when compared to distant relatives. The complexity of the social relations is brought about by this ability to discriminate combined with the longevity of primates. This is a characteristic and discriminative feature of the primate order. Dominance relations occur in every social group of primates. Linear hierarchies of dominance have been developed only once in prosimians (Lemur) and also once in simians (Cercopithecinae). Therefore, liner hierarchies are not typical for primates.     

Inheritance of extrachromosomal ribosomal DNA during the asexual life cycle of Dictyostelium discoideum: examination by use of DNA polymorphisms.

Wild-type isolates of Dictyostelium discoideum exhibited differences in the size of restriction fragments of the extrachromosomal 88-kilobase ribosomal DNA (rDNA) palindrome. Polymorphisms in rDNA also were found among strains derived solely from the NC4 wild-type isolate. These variations involved EcoRI fragments II, III, and V; they included loss of the EcoRI site separating fragments II and V and deletion and insertion of DNA. More than one rDNA form can coexist in the same diploid or haploid cell. However, one or another parental rDNA tended to predominate in diploids constructed, using the parasexual cycle, between haploid NC4-derived strains and haploid wild-type isolates. In some cases, most if not all of the rDNA of such diploids were of one form after ca. 50 generations of growth. Segregant haploids, derived from diploids that possessed predominantly a single rDNA allele, possessed the same allele as the diploid and did not recover the other form. This evidence implies that replication does not proceed from a single chromosomal or extrachromosomal copy of the rDNA during the asexual life cycle of D. discoideum.     

Suppression of cyclic AMP-induced cell excitation in Dictyostelium discoideum by inhibitors of eicosanoid oxidation

Abstract Receptor-mediated stimulation of Dictyostelium cells by the aggregative chemoattractant cyclic AMP leads to a complex excitatory response resulting in chemotaxis and the synthesis and release of cyclic AMP as the relayed chemotactic signal. However, the mechanism of this stimulus-response coupling is not well understood. In this study, we show that a number of compounds, best known as inhibitors of cyclooxygenase activity in mammalian cells, prevent cyclic AMP receptor-mediated cell excitation and cyclic AMP accumulation in aggregation-competent Dictyostelium cells. These observations suggest that some eicosanoid-like compound(s) may be involved in stimulus-response coupling in this organism, as is the case in higher eukaryotic cells.