Microinjection and Micromanipulation: A Historical Perspective.

Microinjection/micromanipulation is more than 100 years old. It is a technique that is instrumental in biomedical research and healthcare. Its longevity lies in its preciseness in mechanical retrieval, or delivery of biological materials, which in some cases is simply necessary or more effective than other retrieval/delivery means. Microinjection is favored for its straightforwardness in transferring contents from micromolecules to macromolecules and from organelles to cells. Microinjection/micromanipulation has been practiced over the century like an art form. Variations in handlings and instruments can be tolerated to a surprising degree with satisfactory outcomes. Throughout the century, microinjection developed as an indispensable tool along with the evolution of biomedical fields: from transgenics to gene targeting, from animal cloning to human infertility treatment, from nuclease-guided genetic engineering to RNA-guided genome editing (Fig. 1). The birth of the CRISPRology rejuvenated microinjection. For microinjection/micromanipulation, the second century has already begun with the early arrival of computerized instrumentation and lately of the high-throughput nanomanipulators potentially operable by artificial intelligence. As we yin-yang both systemic and precision approaches in research and medicine, microinjection will no doubt continue to find its unique place in the future.

[Tibor Péterfi, the founder of micromanipulation]. / Péterfi Tibor, a mikrurgia megalapítója.

Tibor Péterfi (1883-1953) was an eminent and internationally renowned biologist. He made great advances in the field of experimental physiology focusing his cytological research on microscopic examination of living cells. For this task, he created a tool named micromanipulator basing the development of microsurgery and that of cell surgery as well. His histological and cytological researches took their beginning first in Kolozsvár/Cluj (then Hungary, now Romania), where he worked as an assistant of professor István Apáthy then in Budapest where he spent fruitful years under the tutorship of professor Mihály Lenhossék. His scientific career however was broken by the political persecution which followed the fall of the communist revolution in 1919. He emigrated and spent the following decades in Prague, in Jena, in Berlin and in Cambridge. The apogee however of his scientific career proved to be the period he spent in Istanbul as a guest professor of the local university. He returned home only after the war already mortally ill. His illness did not allow him to continue his activity any more. Present article evaluates Tibor Péterfi's scientific achievements based mostly on recent archival researches.

Marshall Barber and the century of microinjection: from cloning of bacteria to cloning of everything.

A hundred years ago, Dr. Marshall A. Barber proposed a new technique - the microinjection technique. He developed this method initially to clone bacteria and to confirm the germ theory of Koch and Pasteur. Later on, he refined his approach and was able to manipulate nuclei in protozoa and to implant bacteria into plant cells. Continuous improvement and adaptation of this method to new applications dramatically changed experimental embryology and cytology and led to the formation of several new scientific disciplines including animal cloning as one of its latest applications. Interestingly, microinjection originated as a method at the crossroad of bacteriology and plant biology, demonstrating once again the unforeseen impact that basic research in an unrelated field can have on the development of entirely different disciplines.

Contributions of blastocyst micromanipulation to the study of mammalian development.

This is a personal account of why the author chose to focus on devising techniques for micromanipulating the blastocyst stage conceptus as a way of investigating early development in mammals. Its aim is to provide insight into what such technical innovations entailed and how they have contributed to present understanding of both embryology and the analysis of gene function in mammals. The ability to dissect and reconstitute mouse blastocysts, and to inject cells or tissue into them, enabled genes to be harnessed as markers for elucidating the lineage of cells and interactions between tissues from the stage when differentiation is first evident. Most importantly, it made it possible to apply clonal analysis to the study of cell fate in mammals. The scope of blastocyst micromanipulation was further enhanced when embryonal carcinoma (EC) cells and, particularly, embryonic stem (ES) cells were found to be able to participate in normal development and contribute to the germ line following injection into the blastocyst.