Mendel discovered the particulate nature of hereditary factors and the rules of their transmission without knowledge of chromosomes. Indeed, much of the classical knowledge of heredity was obtained without reference to any cell structure. When, in the 1920’s, chromosomes were established as the carriers of the linear order of genes, many questions beyond the formal analysis of order and transmission could be tackled. Structural analysis, it was hoped, would soon reveal the mechanism of genetic crossing-over and chromosome replication and chemical studies of chromosomes were expected to give information on the nature of the gene. It turned out, however, that the light microscope could not reveal the organization of chromosomes and that their chemical nature was so complex that it prevented the recognition of the substance of the gene. Progress in chemical genetics became possible only after genetic analysis was extended to viruses and bacteria, organisms which do not have true chromosomes but a much simpler genetic system. Now DNA , already suspected of having something to do with the gene because of its constant association with chromosomes, could be established as the molecular basis of heredity. Above all, it was the recognition of the molecular structure of DNA which provided the understanding of the nature of genetic specificity and its expression in cellular synthesis, and suggested mechanisms for its replication. Viruses and bacteria provided the ideal material for analysis of the basic properties of a genetic system since here the genome consists of a single DNA molecule. It has been recognized for some time that bacteria and the related blue-green algae possess an unusual nuclear organization. The term prokaryotes has been used to distinguish these organisms, from the eukaryote animal and plant cells with typical chromosomes and mitotic division (Dougherty 1957; Ris & Chandler 1963). These terms are useful since they stress a real difference in the complexity of the genetic systems of the two cell types. How has the knowledge gained from the study of micro-organisms helped us in understanding the chromosome? It appears that the basic properties of the genetic system such as the coding for amino acids by the nucleotide sequence of the DNA and its transcription into RNA are alike in prokaryotes and eukaryotes. Nevertheless, the great difference in structural complexity of the two kinds of nuclei must signify some interesting modifications in their operations. It seems to me Important that this difference be recognized in terminology. Since the term chromosome' has been applied to the complex nucleoprotein structure of the ekaryote nucleus, it is unwise to use it also for the DNA molecule of viruses or cteria. I have, therefore, suggested ‘genophore’ as a general term to designate e physical counterpart of a linkage group (Ris 1961). How does a chromosome ffer from the genophore of a bacterial cell? From chemical studies, we know at in addition to DNA a chromosome contains considerable amounts of protein, particularly basic proteins of relatively small molecular weight (histones). In most nuclei, more complex proteins are also associated with chromosomes in variable amounts. What are the roles of these proteins? The chromosome complement of mammals contains about a thousand times as much DNA as a bacterial genophore. Does the histone serve to reversibly coil and condense the long DNA read into a manageable form? It has been suggested that histones act to repress ecific genes. What controls their specific association with DNA and how does is affect chromosome structure? In the light microscope, the chromosome appears ultistranded, and yet during replication it seems to behave in a semi-concervative manner analogous to a single DNA molecule. How can the DNA in a chromosome replicate in the same way as a bacterial genophore since it is many mes longer and in a complex association with protein? Obviously, before we can understand the basic processes of chromosomes, such as their replication and conformational changes during activation of RNA synthesis, we must have a clear understanding of chromosome organization at the molecular level. When the ectron microscope began to reveal the fine structure of cytoplasmic organelles, was hoped that it would soon solve the problems of chromosome organization. While it has shown some interesting details, we must admit that it has not yet answered any of the basic questions. As Porter said some years ago: ‘The nucleus both during interphase and mitosis has come to be regarded as one of the most difficult of biological objects to study by methods of electron microscopy' (Porter 1960). Other methods such as X-ray diffraction and polarizing microscopy have also offered promise here or there without giving final answers to the basic questions. Even though it is as yet impossible to propose a satisfactory model for the chromosome, it might prove useful to review what sort of structures have been revealed by these techniques, how these structures might be related to chromosome function, and what major problems remain unsolved.

No abstract

A family is described in which four children developed cancer affecting different organs: lymphoma, meningeal sarcoma, osteogenic sarcoma, and adenocarcinoma of the cecum. Since there was only one other case of cancer in previous generations of this family, an hypothesis is put forth to explain this unusual aggregation on the basis of recombination of common genes. It is postulated that each parent carried a different combination of genes which, though not associated with increased cancer predisposition in the combinations in which they were present in the parents, due to independent assortment resulted in a combination producing cancer susceptibility in half of the offspring. Such genetic loci could include factors similar to an oncogene which is normally held in control by genes at another locus; thus the dominant oncogene without the dominant controlling genes would make for cancer susceptibility, while the controlling genes without the oncogene would be associated with cancer resistance since two mutations would then be required for malignant development. To explain the occurrence of lymphoma in one of the children in this family, a third set of genes is included in this model-genes affecting immunocompetence, in which the normal allele is dominant. This three locus model has the advantage of being able to explain not only the occasional cancer family, but also the distribution of cancer susceptibility and resistance in the general population.

No abstract

A study was conducted in the confined population of a state school for girls where the majority of students gave a history of past sexual intercourse. As part of a six-year survey for gonorrheal infection, examinations were also conducted for Trichomonas vaginalis and yeast infections. From a total of 6,304 specimens examined, the presence of T vaginalis in 20.3% was revealed.Screening for yeast and Neisseria gonorrhoeae revealed the presence of yeast in 10.4% and N gonorrhoeae in 6.3%. Multiple agents were frequently present (4.3%).The prevalence of T vaginalis infection was determined to be 35.2% in a series of 338 consecutive admissions to the institution. Screening for T vaginalis, yeast, and N gonorrhoeae in the presence of vaginal discharge is recommended.A previous study in a closed population in a state school for girls has shown a gonorrheal preva¬ lence of 11.8% in the years 1965 to 1968, inclusive.1 Reported here are the results of a concurrent study of Trichomonas vaginalis and yeast in¬ fections which has been extended to 1971.The average yearly population of the school is 467. Since the average stay is slightly less than six months, and the capacity of the school is around 250 students, there is at least one complete population change a year. Girls are sent to the school for behavioral problems such as truancy, running away from home, and mis¬ demeanors. The majority of the stu¬ dents give a history of past sexual intercourse and 10% to 15% are preg¬ nant at the time of admission.Although Neisseria gonorrhoeae in¬ fections in the mature woman pri¬ marily involves the cervix, infections with T vaginalis and yeast primarily involve the vagina. In instances in which the students are infected with AT gonorrhoeae alone, the complaint of vaginal discharge is rare. On the other hand, when the infection is caused by T vaginalis the patient will frequently but not always complain about vaginal discharge. The dis¬ charge associated with T vaginalis infection is white, or white tinged with gray or yellow, frothy, bubbly, mucopurulent, and has an acrid odor. Occasionally multiple, punctate, red erosions are seen on the vaginal mu¬ cosa. There is a wide range of clinical manifestations from almost asympto¬ matic to profuse, malodorous dis¬ charge associated with severe pru¬ ritus.Concomitant infection of the urethra in the woman may present a burning sensation on urination and simulate a bacterial urinary tract in¬ fection. When bacterial urinary tract infection is excluded by a standard, urine culture, the student is reexamined for T vaginalis, yeast, and N gonorrhoeae infections. When these organisms are found, specific treat¬ ment is instituted which usually pro¬ duces symptomatic relief. The typical discharge of the Can¬ dida infection is white, curded, and flaky, and sometimes adheres in patches like a plaque to the vaginal mucosa. According to Gardner2 less than 50% of women with symptoms related to yeast infections show evi¬ dence of adhering patches. The infec¬ tion may cause marked pruritus of the vulva...