The first half-century of nuclear transplantation

Abstract

Fifty years after Briggs and King first succeeded in obtaining normal tadpoles from transplanted embryo nuclei in vertebrates, two general principles have emerged from work in amphibia and mammals. One is the conservation of the genome during cell differentiation. A small percentage of adult or differentiated cells have totipotent nuclei, and a much higher percentage of cells committed to one pathway of cell differentiation have multipotent nuclei. The other is the remarkable reprogramming capacity of cell, and especially egg, cytoplasm. The eventual identification of reprogramming molecules and mechanisms could facilitate a route toward cell replacement therapy in humans.

Fig. 1.

Robert Briggs (A; 1911–1983) and Thomas J. King (B; 1921–2000). Photographs were kindly supplied by Marie A. DiBerardino through the courtesy of the Institute for Cancer Research of the Fox Chase Cancer Center, Philadelphia.

Fig. 2.

(A) In Amphibia, nuclear transfer success declines rapidly as cells differentiate. Details are from Briggs and King (6) and Gurdon (20). Feeding tadpoles are more advanced than swimming tadpoles. (B) Nuclear transfer survival in mammals compared with Amphibia. Abnormalities and death occur progressively during development. Original results are from refs. , , and .

Fig. 3.

Adult frog brain nuclei rapidly assume the morphology and synthetic activity of recipient oocytes or eggs a few hours after injection. (A) Brain nuclei of an adult frog. (B) Brain nuclei active in transcription. (C) Condensed chromosomes. (D) Brain nuclei active in replication. Further details can be obtained from Graham et al. (72) and Gurdon (73).