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<p>The first three articles of this series discussed the adoption of cell theory, the chromosomal basis of biological inheritance, and establishment of the basic principles of genetics. This article narrates how cytologists working during the last quarter of 19th century and using ‘primitive’ compound microscopes to study tissues that were fixed and stained with empirically developed tissue-fixation and staining methods generated remarkable information about the many sub-cellular structures, chromosomes, cell division, and macromolecular constituents of cell, including characterization of ‘nuclein’ or nucleic acid. Studies on chromosomes, transformed by replacing histological sectioning with chromosome squashes during the first decade of the last century, identified sex chromosomes. Recognition of karyotype as a phenotypic character led to the emergence of cytotoxonomy. Elucidation of the true nature of ‘giant’ chromosomes in dipteran larval salivary glands (polytene chromosomes) and in oocytes of many organisms, especially amphibians (lampbrush chromosomes), opened new cytogenetic avenues to understand the relation between chromosome structure and gene activity through studies on puffs in polytene chromosomes and the extended lateral loops in lampbrush chromosomes. Polytene chromosomes permitted the construction of the first physical maps of <i>Drosophila melanogaster</i> genes in the 1930s and the recognition of chromosomal polymorphism as an adaptive feature. Development, between the 1920s and 1940s, of macromolecule-specific cytochemical staining and cytophotometric methods, permitted <i>in situ</i> quantification of cellular DNA, RNA, proteins, etc. Such studies revealed species-specific constancy of DNA, but not of protein or RNA, in gametes and zygotes. These results supported that DNA, like the bacterial ‘transforming principle’, transmits genetic information in eukaryotes as well. Improved methods for chromosome preparation from mammalian/human tissues in the 1950s led to the birth of human cytogenetics.</p>

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Tracing the Roots of Molecular Biology

  • 期刊论文

  • 发表日期：

    2025年8月18日

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  • Subhash C. Lakhotia

摘要

The first three articles of this series discussed the adoption of cell theory, the chromosomal basis of biological inheritance, and establishment of the basic principles of genetics. This article narrates how cytologists working during the last quarter of 19th century and using ‘primitive’ compound microscopes to study tissues that were fixed and stained with empirically developed tissue-fixation and staining methods generated remarkable information about the many sub-cellular structures, chromosomes, cell division, and macromolecular constituents of cell, including characterization of ‘nuclein’ or nucleic acid. Studies on chromosomes, transformed by replacing histological sectioning with chromosome squashes during the first decade of the last century, identified sex chromosomes. Recognition of karyotype as a phenotypic character led to the emergence of cytotoxonomy. Elucidation of the true nature of ‘giant’ chromosomes in dipteran larval salivary glands (polytene chromosomes) and in oocytes of many organisms, especially amphibians (lampbrush chromosomes), opened new cytogenetic avenues to understand the relation between chromosome structure and gene activity through studies on puffs in polytene chromosomes and the extended lateral loops in lampbrush chromosomes. Polytene chromosomes permitted the construction of the first physical maps of Drosophila melanogaster genes in the 1930s and the recognition of chromosomal polymorphism as an adaptive feature. Development, between the 1920s and 1940s, of macromolecule-specific cytochemical staining and cytophotometric methods, permitted in situ quantification of cellular DNA, RNA, proteins, etc. Such studies revealed species-specific constancy of DNA, but not of protein or RNA, in gametes and zygotes. These results supported that DNA, like the bacterial ‘transforming principle’, transmits genetic information in eukaryotes as well. Improved methods for chromosome preparation from mammalian/human tissues in the 1950s led to the birth of human cytogenetics.