The Epigenetics Revolution

We could hypothesise that the reason why mammals all have a mother and father is because that’s what we need to introduce two haploid genomes to one another, to create a new cell with a full complement of chromosomes. Certainly it’s true that this is what normally happens but this model would also imply that the only reason why biologically we need a parent of each sex is because of a delivery system.

Conrad Waddington’s grandson

In 2010 Professor Robert Edwards received the Nobel Prize in Physiology or Medicine for his pioneering work in the field of in vitro fertilisation, which led to the so-called test tube babies. In this work, eggs were removed from a woman’s body, fertilised in the laboratory, and re-implanted back into the uterus. In vitro fertilisation was hugely challenging, and Professor Edwards’ success in human reproduction was built on years of painstaking work in mice.

This mouse work laid the foundation for a remarkable series of experiments, which demonstrated there’s a lot more to mammalian reproduction than just a delivery system. The major force in this field is Professor Azim Surani, from Cambridge University, who started his scientific career by obtaining his PhD under the supervision of Robert Edwards. Since Professor Edwards received his early research training in Conrad Waddington’s lab, we can think of Azim Surani as Conrad Waddington’s intellectual grandson.

Azim Surani is another of those UK academics who carries his prestige very lightly, despite his status. He is a Fellow of the Royal Society and a Commander of the British Empire, and has been awarded the prestigious Gabor Medal and Royal Society Royal Medal. Like John Gurdon and Adrian Bird, he continues to break new ground in a research area that he pioneered over a quarter of a century ago.

Starting in the mid 1980s, Azim Surani carried out a programme of experiments which showed unequivocally that mammalian reproduction is much more than a matter of a delivery system. We don’t just need a biological mother and a biological father because that’s how two haploid genomes fuse to form one diploid nucleus. It actually matters enormously that half of our DNA comes from our mother and half from our father.

Figure 7.1 shows what a just-fertilised egg looks like, before the two genomes meet. It’s simplified and exaggerated, but it will serve our purpose. The haploid nuclei from the egg and the sperm are called pro-nuclei.

^{Figure 7.1 The mammalian egg just after it has been penetrated by a sperm, but before the two haploid (half the normal chromosome number) pronuclei have fused. Note the disparity in size between the pronucleus that came from the egg, and the one that originated from the sperm.}

We can see that the female pronucleus is much bigger than the male one. This is very important experimentally, as it means that we can tell the different pronuclei apart. Because we can tell them apart, scientists can transfer a pronucleus from one cell to another, and be certain about which one they transferred. They know if they transferred a pronucleus that came from the father’s sperm (male pronucleus) or from the mother’s egg (female pronucleus).

Many years ago Professor Gurdon used tiny micropipettes to transfer the nuclei from the body cells of toads into toad eggs. Azim Surani used a refinement of this technology to transfer pronuclei between different fertilised eggs from mice. The manipulated fertilised eggs were then implanted into female mice and allowed to develop.

In a slew of papers, mainly published between the years of 1984 and 1987, Professor Surani demonstrated that it’s essential to have a male and a female pronucleus in order to create new living mice. This is shown graphically in Figure 7.2.