Nature’s operating system – an essay by Christopher V.E. Wright, D.Phil.  pg. 3

These were followed by Sydney Brenner, Robert Horvitz and John Sulston (2002), honored for their studies on organ development and programmed cell death in nematode worms, and Richard Axel and Linda Buck (2004), for discovering the elegant molecular mechanisms of mammalian olfaction.

Among the most recent Nobel laureates: Andrew Fire and Craig Mello (2006), whose findings in C. elegans on gene regulation by short RNAs sparked another revolution in methods for manipulating gene activity; and Mario Capecchi, Martin Evans and Oliver Smithies (2007), recognized for their terrific work on how to engineer targeted mutations in genes using embryonic stem cells.

Discoveries by developmental biologists regarding stem cells stand among the most spellbinding. In their full incarnation, stem cells have almost unlimited proliferation capacity and long lifespan, and their “pluripotency” enables them to put out many different cell types. They have, especially as embryonic stem cells, led to much scientific, political, and ethical/moral debate.

Because we are now starting to find out how to control the differentiation of stem cells down specific paths, which could herald the large-scale production of material suitable for cell-based therapies for many kinds of human disease, developmental biologists of all ages (professors and trainees) have a responsibility to get properly informed and to teach others on these issues.

Early stem cell work involved trying hard to generate tissue culture dish models for embryonic development, and it was essentially this track that has led to our ability to manipulate the genome in stunning ways. In mice, one can now choose from a delightful smorgasbord of ways to manipulate any chosen gene. These include mutations to inactivate it or to engineer individual amino acid alterations to create models of human syndromes, or to add a fluorescent protein tag that allows us to watch the gene turning on or off in the embryo, and even to pull the cells out very selectively for analysis in vitro.

Sense of wonder

There is a justifiable current furor among scientists over the discovery that a special set of just three or four genes can impart the property of pluripotentiality to mature, differentiated cells. This property is usually associated with embryonic cell types. Defining how the necessary changes in gene activity are effected at the level of chromatin organization in the nucleus is an extremely active area of research, with implications at many levels.

Such epigenetic regulation and reprogramming is really attractive, given the prospect of being able to induce regeneration from a patient’s own cells to replace those destroyed by Alzheimer’s, muscular dystrophy, diabetes, or other diseases. These sorts of discoveries begin to place true regenerative medicine within reasonable grasping distance.

Developmental biology also connects with understanding and controlling cancer. It was a genetic analysis in fruit flies that led eventually to the discovery of a lipid-decorated intercellular signaling protein called Hedgehog, which is also present in mammals, and the dissection of the signaling mechanism by which cells can detect and respond to it.

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