Monday, October 8, 2012

Stem cell researchers awarded Nobel Prize

This year's Nobel Prize for medicine has been awarded. Last year, the prize was given to researchers in the field of immunology, who discovered the function of an important class of receptors used for the body's response against foreign invaders. For 2012, two scientists working on stem cells have to share the prize, and deservedly so. Their work pioneered the use of stem cells for medicinal purposes, and their work laid the foundation for artificial creation of stem cells, which means the ethically troublesome embryonic stem cells need not to be used anymore, and cloning, which also has important implications for medicine.

The winners
John Gurdon, from the UK, and Shinya Yamanaka, a Japanese citizen, have won the prize, and they have both done research on stem cells, albeit on different subjects within the field. Gurdon, who has a remarkable hair style, is the older of the two, having reached the respectable age of 79 years this month. Yamanaka is relatively young, having celebrated his 50th birthday one month ago.

Naturally, an article about Nobel Prize winners deserves an explanation of their work, starting with Gurdon. He pioneered the field of cloning by using genetic material from a 'mature' cell, and putting that in the 'shell' of an unfertilised egg. Normally, an egg contains all the necessary information to form a fully-fledged organism, once it is penetrated by a sperm cell, and this process works in pretty much the same way for many animals, including humans. By removing the original material from the egg and replacing it with the content of a mature cell, Gurdon discovered one of the first techniques used for cloning. Basically: you can use one of your own cells, put it into a ready-made egg cell, and you could create a clone of yourself. While that would be unethical to do in humans, scientists succeeded in the cloning of a sheep, now known as Dolly, though Gurdon did his work with frog cells.
An overview of the cloning process that lead to Dolly. The nucleus (containing the DNA) is removed from the egg cell, leaving an 'empty shell'. Another nucleus, taken from one of the cells from the to-be-cloned animal, is put inside instead.
Stem cell creation
The work of Yamanaka is similar, though there are important differences. His lab found a way to create stem cells from adult, fully differentiated cells. Normally, it is not possible to give a mature cell the characteristics of a stem cell, because once committed to a certain developmental pathway, there is no turning back. That means stem cells need to remain stem cells in order to keep their regenerative capacities. This is also why embryonic stem cells are the most versatile: they arise at the earliest time-point in the development of an organism, and therefore have the most differentiation options.

Yamanaka found a way to direct a cell to reverse its development and revert back into a stem cell. His technique, dubbed induced pluripotency, works by genetically modifying a cell, introducing the expression of just four genes that completely revert the cell's behaviour to that of a stem cell. These induced pluripotent stem cells were shown to be almost as versatile as their embryonic counterparts, but proved to be more safe for use in the clinic. Nowadays, only three of the four genes are used for the modification process, or sometimes one of them is replaced by another gene, but the basic principle remains the same as originally published by Yamanaka in 2006, which is a relatively short while ago.
A simple schematic showing the formation of iPS cells. Starting off with adult cells that cannot differentiate into anything, transfection with viruses containing the necessary genes results in radically altered behaviour, giving rise to stem cell-like cells. They have the capability to differentiate into all three key cellular layers, basically being able to give rise to all cell types in the body.
While stem cells and cloning have been hallowed for years, not many new therapeutics have found their way into the clinic so far. Getting stem cells to work in a safe and efficient way proved to be harder than originally thought, though we are seeing some fruitful attempts coming up. Examples include the discovery of an important master molecule and a key signalling pathway, or the ability to repair damaged hearts. In the lab, we have already shown to be capable of creating all kinds of important tissues, usable for therapeutics, including bone and liver, possibly suitable for transplantation in the future.

Giving the 2012 Nobel Prize for medicine to these two gentlemen is a well-made choice by the organizing committee. Cloning and stem cells are two topics that currently dominate the headlines when it comes to novel technology in medicine, and the work by Gurdon and Yamanaka has been ground-breaking. They both have, independently, developed techniques that are still used, albeit in adapted form, today in order to create the next generation of therapies.

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