Monday, October 22, 2012

A few Nobel Men


As kids, we study a wide range of subjects in school, from English to Social Studies and Science and even Music and Dance. But as we progress to Senior School, we choose a specific “Group”, be it Biology, Commerce or Computer Science. When we move into college for graduate and post graduate degrees, our education becomes still more specialized. We dig deeper into a specific subject and soon reach a state where we forget the basics of the other subjects we learnt as kids. For most of us, this signifies a point of no return, a stage when we are already lawyers,  engineers or doctors and there is no way to go back in time to make a drastic career change.
This social experience mirrors what was always believed to happen in nature. We start our life as a single cell embryo which divides to give rise to cells that are capable of forming the entire organism. These multi-potential cells are called stem cells (specifically embryonic stem cells as they are found in the embryo). But with each subsequent division, the new cells become highly specialized, committed to performing unique functions. Some of the cells mature into muscle cells, some become fat cells, and some turn into nerve cells and together make a functional organism, whether it is a mouse or a human being. 
One of the most interesting questions in Biology was, like many individuals in their career path, have these cells too reached a point of no return?  Can they no longer give rise to any other cell type except the kind they are committed to form? Or can the mature adult cells be reprogrammed to revert to their earlier uncommitted state?
This year’s Nobel Prize for Physiology or Medicine, honors two scientists who answered the latter question with a resounding “Yes, the adult human cells are indeed reprogrammable! “ Sir John B. Gurdon of U.K and Shinya Yamanaka of Japan have been awarded the 2012 prize for the discovery that mature cells can be reprogrammed to become pluripotent (cells capable of giving rise to many different kinds of cells).
Remember Dolly, the sheep, which made “cloning” a household word in the early 90’s?  She was created by a process of nuclear transfer where the nucleus of the cell, which contains the entire genetic information of the organism, was taken out of an adult sheep cell and placed inside an enucleated egg cell, to form an embryo.
John Gurdon performed such a nuclear transfer in 1962. For the first time he showed that the nucleus of a mature frog intestinal cell, when placed inside an egg cell which had its nucleus removed, could reprogram itself and regain its non- specialized nature. The reprogrammed cell divided like a regular embryo and successfully produced live tadpoles, paving the way for research that led to the creation of Dolly. This revolutionary experiment disproved the dogma that adult cells are irreversibly committed into specialized cell types. 
But nuclear transfer into enucleated egg cells is a difficult process.  It also raises ethical questions about using human egg cells and playing God by creating human embryos that have to be destroyed to obtain the stem cells from them. In a quest to find an alternate route to reprogram mature adult cells into pluripotent stem cells, Shinya Yamanaka resorted to a totally different approach. He identified genes that are responsible for the non- specialized nature of embryonic stem cells. He then expressed these genes in the mature adult cells. And viola! He could convert the mature committed cells into immature stem cells that had the potential to give rise to many different cell types. The creation of these cells, termed induced pluripotent stem cells (iPSCs), first published in 2006, marked a significant development in cellular biology.
Together, these two discoveries changed our understanding about development of cells and by extension, the whole organism. They opened up the tantalizing prospect of creating different cell types including skin and liver from adult cells. Imagine the possibility of regenerating any tissue that has been lost by accident or disease! The iPSCs created from diseased individuals would also be of great value in screening drugs for treatment.
Of course, more research has to be carried out into the safety and practicality of using these cells in humans for therapy and improved methods have to be devised for creating these cells. But today, let us celebrate two individuals who have been bestowed with one of the highest honors for their contributions to the advancement of science.