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. 2015 Jul 30;6(3):e0023.
doi: 10.5041/RMMJ.10208.

The Egg and the Nucleus: A Battle for Supremacy

Free PMC article

The Egg and the Nucleus: A Battle for Supremacy

J B Gurdon. Rambam Maimonides Med J. .
Free PMC article


This brief introduction is followed by a published version of my Nobel Laureate lecture, re-published herein with the kind permission of the Nobel Foundation. Much has happened since my original research, for which that prize was awarded. Hence, I am pleased to offer a few thoughts about the future of my research and its possible impact on humankind.Although the original work on nuclear transfer and reprogramming was done over half a century ago, advances continue to be made. In particular the Takahashi and Yamanaka induced pluripotent stem cells (iPS) procedure has opened up the field of cell replacement to a great extent. Now, more recently, further advances make this whole field come closer to actual usefulness for humans. Recently, in the UK, the government approved the use of mitochondrial replacement therapy to avoid the problems associated with genetically defective mitochondria in certain women. Although the House of Commons (members of Parliament) and the House of Lords had to debate and discuss whether to allow this kind of human therapy, I was very pleased to find that both bodies approved this procedure. This means that a patient can choose to make use of the procedure; it does not in any way force an individual to have a procedure that they are not comfortable with. In my view, this is a great advance in respect to giving patients a choice about the treatment they receive. I am told that the UK is the first country in the world to approve mitochondrial replacement therapy.Now that the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPr) technology is being widely used and works well, one can foresee that there will be those who wish to use this technology to make genetic changes to humans. For example, if a human has a gene that makes it susceptible to infection or any other disorder, the removal of that gene might give such a person immunity from that disease. If this gene deletion is done within the germ line, the genetic change will be inherited. However, one can imagine that various people will strongly object and say that this technology should not be allowed. I would very much hope that various regulatory bodies, governments, etc. will allow the choice to remain with the individual. I can see no argument for such bodies to make a law that removes any choice whatsoever by an individual.


Figure 1
Figure 1. Design of a Somatic Cell Nuclear Transfer Experiment using Unfertilized Eggs as First Designed by Briggs and King for Rana pipiens and as used Subsequently in Xenopus.
In Rana, enucleation is by hand with a needle, and in Xenopus by ultraviolet light irradiation.
Figure 2
Figure 2. Survival of Nuclear Transplant Embryos in Rana pipiens and Xenopus laevis
Even advanced donor cells from the endoderm have nuclei which can sometimes yield normal individuals after nuclear transfer (from Briggs and King [Rana] and Gurdon [Xenopus]6).
Figure 3
Figure 3. Xenopus Egg Images
The Xenopus egg is surrounded by a dense elastic jelly so that it is not possible to penetrate into the egg cytoplasm with a micropipette, unless the jelly is removed or denatured by ultraviolet light. (A) Side view. (B) “Animal” pole; the white area in the middle of the black area is where the egg chromosomes are located. (C) If the egg is not de-jellied, a micropipette depresses the jelly coat, eventually dragging the pipette, still surrounded by jelly, through the egg without entering the cytoplasm (D).
Figure 4
Figure 4. Michail Fishberg
Born in St Petersburg, educated in Switzerland and PhD under E. Hadorn. The education lineage traces back from Hadorn to Baltzer to Boveri. MF was my graduate supervisor in Oxford, England, from where he moved to Geneva.
Figure 5
Figure 5. A Nucleolar Genetic Marker for Xenopus laevis (Elsdale et al.11)
Heterozygotes of the one-nucleolated strain have only one nucleolus per diploid nucleus (left), compared to the wild-type 2-nucleolated form most of whose nuclei have two nucleoli (right). The one-nucleolated strain has a deletion of ribosomal genes on one chromosome.
Figure 6
Figure 6. A Clone of Albino Male Frogs Obtained by Transplanting Nuclei from Cells of an Albino Embryo to Enucleated Eggs of the Wild-type Female
The albino frogs are genetically identical and will accept skin grafts from each other.
Figure 7
Figure 7. Epigenetic Memory in Nuclear Transplant Embryos
Nuclear transplant embryos derived from muscle nuclei were grown to the blastula stage, and then depleted of the mesoderm region (muscle lineage). The remaining regions (neurectoderm for nerve/skin cells and endoderm for intestine lineages) express the muscle gene marker MyoD to an excessive extent in about half of all such embryos.
Figure 8
Figure 8. Survival of Nuclear Transplant Embryos in Xenopus and the Mouse.
Figure 9
Figure 9. The Xenopus Oocyte
The Xenopus oocyte grows in the ovary from a germ cell over many months while it is in first meiotic prophase. When fully grown it can respond to hormones, such as progesterone, to complete first meiosis and arrest in second meiotic metaphase. Once fertilized, it progresses to the blastula stage in 8 hours and somatic lineages already start to appear.
Figure 10
Figure 10. The Germinal Vesicle in the Xenopus Oocyte
A Xenopus oocyte has a huge (420 μm diameter) germinal vesicle, which includes its tetraploid chromosome set. After completion of meiosis, the germinal vesicle contents are distributed to the egg and subsequently to the embryo.
Figure 11
Figure 11. Multiple Somatic Nuclei can be Injected into the Germinal Vesicle of an Oocyte
Left: Whole oocyte. Right: Germinal vesicle.
Figure 12
Figure 12. Somatic Nuclei Injected into the Germinal Vesicle of an Oocyte Transcribe Genes that are Quiescent in the Donor Cells but Are Rapidly Transcriptionally Activated
The most specialized donor nuclei (mouse thymus) showed temporal resistance to transcriptional activation.

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