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Glucksmann ('51) observed that during normal mammalin ocular morphogenesis large numbers of cells become necrotic and are resorbed within the eye rudiment prior to and during invagination of the optic cup. Silver and Hughes ('73) observed that these resorptions are largely confined to the ventral aspect of the optic rudiment where the optic fissure subsequently forms. Evidence for the role of cell death during fissure formation and other morphogenetic events during eye development has remained unclear, however, since the quantity of degenerate cells cannot be selectively controlled in developing tissue by experimental means (Saunders, '66). Chase et al. ('41a) described a congenitally anophthalmic strain of mice in which, he proposed, retarded growth of the eye vesicle and the consequent failure of lens induction result in approximately 90% eyeless and 10% microphthalmic neonates. Upon reexamination of a sequence of embryos of the eyeless strain it was observed that during the earliest stages of ocular morphogenesis the regular sequence of necrotic loci, which Silver and Hughes ('73) have described in rat and other mammalin embryos, is entirely lacking. Our observations suggest that the first recognizable divergence between the morphology of timed mutant (strain zrdct-an) and control embryos (strain C57BL/6J) occurs during apposition of the optic vesicle and surface ectoderm but prior to the development of the retinal thickening and lens placode. In control embryos mesenchyme which becomes entrapped between the prospective retina and lens becomes necrotic and is resorbed. Conversely, in eyeless embryos the surfaces of the presumptive retina and lens, while closely apposed, are separated by variable numbers of mesenchymal cells which remain viable and can undergo mitoses throughout development. The failure of mesenchymal cells to degenerate may lead to the reduction in size of both retina and lens primordia. Contrary to Chase's ('41a) observations, in all anophthalmic embryos contact between the optic vesicle and lens epithelium is eventually established and a lens of variable size is induced. In most cases, however, the lens is displaced from the eye chamber by proliferation of the mesenchymal cell mass and the optic rudiment is subsequently resorbed. In the remaining embryos which presumably will become microphthalmic the lens reaches a critical dimension and is retained within the eye cup. In them, although cell death is absent from within the developing eye vesicle and cup, invagination can proceed as far as the retinal fissure stage. However, the optic fissure does not form. These observations suggest that there may be a relationship between morphogenetic cell death, formation of the optic fissure, and the production of severe congenital eye defects.

Experimental work on abnormal conditions of incubation in the chick has been undertaken to acquire a scientific approach to malformations. More precise experiments on causing abnormalities had a common origin with experimental embryology. Progress in experimental teratology during the last 50 years is reviewed in a commentary on the 4 principles formulated by Stockard in 1921. The results of cytogenetical studies in man and in other organisms have led to the tracing of some relationships between them. Present knowledge concerning malformations of the neural tube, originating either experimentally, spontaneously, or phenotypically, has been presented and the teratological implications of some recent theories on the expression of the genotype are discussed in particular reference to problems of hormones as teratogens, the implication of carbohydrate metabolism, and teratogenesis. It is speculated that teratogenesis is possibly related to cationic balance in early development and that 1 factor retarding progress in the understanding of malformations is the tendency toward the development of teratology in an adequately close relationship with other branches of cell biology.

1. 1. A magnetic method is described for the study of the consistency of the protoplasm of living cells in tissue cultures. 2. 2. Such protoplasm is not purely viscous, but has elastic properties. 3. 3. The order of magnitude of the modulus of rigidity is 10 2 dynes/cm 2 . 4. 4. There is evidence of thixotropic behaviour. 5. 5. The bearing of these results on current theories of protoplasmic structure is discussed.

In the development of the vertebrate nervous system not all the neuroblasts complete their development into neurones. In the lumbar ventral horns of the larvae of Xenopus laevis, the number of viable and degenerating cells has been counted throughout development. Given an estimate of the duration of cell death, the total number of cells which degenerate can be calculated; for every cell which finally differentiates, eight or nine die during development. The death rate of cells in the ventral horns can be reduced or abolished by X rays at a dosage of 80–160 r. This arrest may persist for nearly three weeks with relatively young tadpoles, but for only a few days with older animals. When larvae are irradiated near the maximal period of normal degeneration, the arrest of degeneration is evident within a few hours after treatment. The effect is thus shown to be more than a secondary consequence of a general halt in development.

In the early years of this century debate concerning the development of nerve fibres became more intense. During the previous decade, following the developmental studies of His (1883, 1886) and the early embryological studies of Ramon y Cajal (1890), the neurone theory as proclaimed by Waldeyer in 1891 seemed assured of victory; but when, with Apathy and Bethe, new technical developments diverted attention from the whole neurone to its apparent constituents, the neurofibrillae, the simple concept of the outgrowth of the nerve fibre became enmeshed in complexity. Methods for their impregnation with silver were soon elaborated (Bielschowsky, 1904; Ramon y Cajal, 1903), and Held (1907) affirmed that a network of neurofibrillae preceded the appearance of the definitive nerve process. This claim became associated with the much older views of Hensen (1864, 1876) that protoplasmic strands were the forerunners of the nerve fibres and constituted a ground plan for the later development of the peripheral nervous system.

1. An apparatus is described for the measurement of the pressure in the chorioallantoic artery of the chick embryo. 2. Data are given of such measurements ranging in time from the second to the nineteenth days of incubation. 3. Some measurements are also given of the arterial pressure of the chick within the first five days after incubation.

The interest of the writer was first directed towards the study of the blood vessels of the head by comparing a dissection of the head arteries of the pig with one of the corresponding vessels in the pigeon. Both systems of vessels include a rete mirabile, but whereas that of the pig interrupts the internal carotid just before its entrance into the sella turcica, that of the pigeon corresponds to the temporal rete of the chick described in the present communication, and is found in the orbit in no immediate connection with the internal carotid. It was difficult to see how acommon functional explanation could be applied to both these retia. My attention was then drawn to the work of Shellshear, who from comparative studies of the distribution of the encephalic arteries in adult material had advanced certain hypotheses, summarized later in this communication, regarding the way in which blood vessels were supposed to develop. The most direct way of testing Shellsi-iear s hypotheses seemed to be that of studying intensively the development of the blood vessels in a single form. The examination of the literature of the development of the vascular system revealed the fact that hardly ever, if at all, had the development of arteries and veins been studied at the same time. Moreover, through the development of technique for the injection of embryonic material, it had been shown in many forms that a preliminary stage of capillary plexus is antecedent to definitive blood vessels. Yet although comparatively early embryos of birds and mammals had been studied by this means, no work had been done on any form in following the development of the blood vessels from the earliest stages to the adult condition. For the chick, Miss Sabin had given an account of the development of the blood vessels from the earliest stages up to the twenty-nine somite stage, Sabin (1917). It was decided to attempt to continue this account of the development of the blood vessels of the chick for the remainder of the embryonic period. I am grateful to Professor J. Stanley Gardiner, F. R. S. , and to Mr. C. Forster-Cooper for the privilege of working in the Zoological Department and the Museum of Zoology respectively of the University of Cambridge. I am further indebted to Mr. C. Forster-Cooper for much help and to Dr. S. M. Manton for her never failing advice and assistance in many matters of histological technique, and in the preparation of illustrations. Mr. G. R. de Beer was good enough to offer advice on certain matters, as was Mr. W. J. Heasman on the subject of the preparation of transparencies.

Serial sections of embryonic rat eyes were stained with hematoxylin and eosin, quantified (by counting pycnotic and viable nuclei), reproduced by camera lucida on wax plates, and moulded into reconstructions in order to study the normal progression of cellular death during morphogenesis. At least nine distinct necrotic loci (A through I) can be distinguished. Immediately following contact between the retina and surface ectoderm (day 11) degenerating cells were observed in (A) the ventral extent of the optic vesicle, beginning in the mid-retinal primordium and continuing ventrally in the optic stalk, (B) in the rostral optic stalk base, and (C) in the surface ectoderm encircling the early lens placode. No degeneration was observed in the dorsal half of the presumptive retina, in the entire pigment epithelium, or in the lens placode proper. During day 11.5 the lens placode thickens and forms a degenerating locus (D) in its ventral portion opposite the underlying pycnotic zone in the retina (A). During day 12 the ventral pycnotic zone (A) divides into two subunits (A1 and A2). Invagination of the lens displaces its marginal and ventral components (C and D) so that they come to occupy the lens pore area and presumptive corneal epithelium. Simultaneous invagination of the retinal rudiment juxtaposes the pigment epithelium which concurrently forms a necrotic area (E) adjacent ventrally to that in the retina (A1). Degeneration appears in the caudal optic stalk (I). The density of viable cells decreases adjacent to pycnotic areas in the retina and pigment epithelium and increases within these death centers. During day 13 the optic fissure forms within the subunits of the ventral pycnotic zone (A1 and A2). Degenerations are seen in the dorsal optic stalk (F) and in the walls of the optic fissure (G and H). Throughout these stages necrosis appears only in those portions of the eye rudiment where invagination is either retarded or completely absent. In part, these observations suggest that cell death serves (1) to retard or inhibit invagination within death centers, (2) to integrate the series of invaginations which mould the dorsal optic cup and optic fissure, (3) to assist formation of the pigment epithelium monolayer, and (4) to orient the lens vesicle within the eye cup. The spatio-temporal relationship between necrotic loci suggests that pycnotic cells in the retina may influence their production in the lens and pigment epithelium. Preliminary observations on the mouse, pig, and human substantiate those on the rat.

Postnatal maturation of nonmyelinated fiber bundles (Schwann bundles) was studied in the sciatic nerves of Snell's dwarf mice. The homozygous recessive of this strain has been previously shown to be characterized by multiple pituitary hormone deficiencies and secondary hypothyroidism. In the normal littermates a reduction occurred between 10 and 14 days in the number of fibers per fascicle, or subdivision, of each Schwann bundle, and by 26 days nearly all of the axons were separately embedded in cytoplasmic furrows of their associated Schwann cells. Only a few large fascicles were seen in normal sciatic nerve specimens at 26 and 50–53 days. In contrast, fiber bundle fascicles in the mutant nerves were still represented, even at 50–53 days, by numerous tightly-packed axons, as seen in the immature nerves at 10–12 days post-partum. On the basis of the dwarf's physiological background, these results suggest an involvement of the endocrine system during later stages of peripheral nerve maturation. The possible mechanisms affected by postnatal endocrine deficiency and thereby leading to delayed segregation of nonmyelinated fibers within Schwann bundles are discussed.

DURING recent months, several items have appeared in NATURE which were concerned at least in part with the topics of warfare, past or future. This may be taken as an expression of the realisation that science has given modern warfare its catastrophic character. While scientific investigators cannot be held directly responsible, many of them are coming to feel that they cannot remain indifferent to the indirect effects of their work.

IN the spinal cord of larval Anura, the motor cells which innervate the muscles of the hind limbs form ventral horns distinct both in position and time of appearance from the series of primary motor cells whose axons run to the trunk muscles. In the tadpole of Xenopus laevis, there are about 4,000 ventral horn cells at the time of their differentiation from the mantle layer of the cord, a number which has fallen to 1,200 by metamorphosis some eight weeks later1. ‘Histogenic cell degeneration’2 accompanies the differentiation of these neurones, but on a scale much beyond that required merely to reduce their number to the adult-level. It seems that, for every ventral horn cell that persists, some eight or nine undergo cell death during development. Differentiation of the ventral horn is thus accompanied by a continuous turnover of the constituent neuroblasts.

WHILE we appreciate the fulness of the treatment which has been accorded to our book ” The Protection of the Public from Aerial Attack”, we should be grateful for the opportunity of commenting on certain points in the review in NATURE of April 10, p. 606. Regarding the purpose of the book, General Foulkes says, ” It suggests no better defensive measures than those recommended by the Home Office”. Better methods are not lacking, and our object simply was to provide some scientific data concerning the proposed precautions—because no such data had been published and we felt that the unsupported statements of Government spokesmen concerning their efficiency were no substitute for scientific fact.

A decision tree to place sounds into 10 vowel categories has been constructed in a manner described earlier [Li, House, and Hughes, J. Acoust. Soc. Amer. 44, 390(A) (1968)]. Training data consisted of spectral samples from the central portions of the stressed vowels in 325 utterances spoken by two talkers. The process independently arrived at the same decision tree for both talkers. To test the effects of context on vowel separation using such a tree together with its separating hyperplanes, three additional sets of utterances were processed without further training: (1) new repetitions of portions of the hoə'CVC list, (2) a list of English CVC words, and (3) connected speech containing the CVC words from (2). The errors (7%) made on material essentially identical to the training data can be interpreted as inherent in this method; the errors (11%) made on the CVC words can be attributed to consonantal environment; errors made in continuous speech are mainly due to stress reduction. [This research was supported in part by the Air Force Cambridge Research Laboratories.]