Note: This article is intended for people from non scientific background
The 2012 Nobel Prize in Physiology or Medicine is won by Sir John B. Gurdon from the Gurdon Institute, Cambridge, United Kingdom and Shinya Yamanaka from the Kyoto University, Kyoto, Japan. They got the prize for their work in Stem cell research.
According to the website Nobelprize.org, the prize is- “for the discovery that mature cells can be reprogrammed to become pluripotent”
For a person with no scientific background in life science, it will be difficult to understand what the above quoted statement means and the social implications of their research works. So, in this article I try to explain in the simplest way I can, the deep meaning of that statement. This article is intended for people from non-scientific background and hence Science geeks will find this article too simple and straightforward with least number of technical terms. Sorry, that was intended.
“For the discovery that mature cells can be reprogrammed to become pluripotent“
1) Mature cells
Understanding these 3 terms and their mutual relation will help you get a clear idea about what this is all about.
We need to start from the beginning. From the very first cell from which you and me grew up-The zygote. The sperm from father and the egg from mother, both with half the number of their chromosomes in it, fused together and formed the zygote, which by then has the entire chromosome set (chromosomes are basically DNA) ,and from that zygote, through a number of cell division cycles, the fully grown organism evolve. The process may sound straight forward- cells keep dividing until the required number of cells is made and there you are! No, it’s not that simple, it’s not even remotely simple; the entire process from the formation of zygote to a fully grown human being is controlled and managed by thousands of complicated steps, involving many bio molecules and countless biological pathways.
Now, as you know, you are made up of cells. Every part of your body are made of different class of cells. I am not referring about muscle cells, skin cells like that, but, cells in your body differ in their properties or in their “capabilities”. Throughout your development, the cells in your body has different “cell fate”. Cell fate means each cell is told “what it has to become”. The zygote- which is a cell, is a “totipotent” cell. It means, the cells of entire organism can be developed from those cells. Making it simpler, from a totipotent cell, by cell division all kinds of cells of the organism can be produced. The zygote divides into 2, then to 4, then to 16, then to 32 so on. Up to the 16 cell stage, all the cells are totipotent, i.e. take any cell out of the 16, it can be differentiated into any kind of organ in our body or even the entire organism.
The next classes of cells are Pluripotent cells. It is almost like the totipotent cells with the exception that it cannot produce extraembryoic tissues ( Don’t bother about what it is, just understand that, from pluripotent cells you can get any type of cells found in an adult.) Means, from a pluripotent cell, you can give rise to a nerve cell or a blood cell or a muscle cell like that. Where do you find pluripotent cells? A simple answer is after the 16 cell, when the cell divides and forms 32 cell groups, these cells are now pluripotent and thus many cells in the embryonic stage are pluripotent in nature. So, embryonic stem cells- which is causing a lot of ethical debates is pluripotent in nature.
The 3rd important class of cell you need to know is the multipotent cell. Right now, inside your body there are multipotent stem cells. Multipotent stem cells can “transform” themselves to a restricted class of cell types. For example adult stem cells- the stem cells which are found now inside your body, they are multipotent. They can be transformed only into a specific type of cell. So, HSC or Hematopoietic stem cells can turn into different kinds of blood cells. So, every time your blood cells are replenished, remember it is the HSC which is in action.
How does our cells know what to become and what not to? “To be or not to be, that is the question!”
The answer is programming. Not the computer programming, but biological programming! As I said before, cells has their “fate”. And this fate is controlled by “genes” . Every process that takes place in our body is controlled by genes- our genetic material-the DNA. Specific genes direct the production of specific proteins and the permutations and combinations of these proteins along with other regulatory mechanisms decide/direct each cell to what it has to become. So, by the term “programming”, think that, a series of bio molecules present in our body tells these cells about what it should become and the cells oblige to what these molecules say (normally!). It has been though that, this programming is uni directional. i.e, from the simplest undifferentiated cell, as it grows up, to specialized cells in adults. i.e if a cell is told to become a skin cell, then that cell will become part of skin cell. No going back and thinking, okay, i dont want to be a skin cell, tell me to become a muscle cell. We thought that was not possible. But the experiments by this year’s Nobel laureates and other scientists proved that, the process can be reversed! Once, a cells fate is decided, IT CAN BE changed. That is, they showed how to “reprogram” the cells so that, it can become other cell types. Now mature cells are those cells whose fate is already decided. So, almost all adult cells are mature cells, and embryonic cells are NOT mature cells.
Let us see, what these 2 scientists have achieved. Do keep in mind that these 2 scientists DID NOT work together. The experiments conducted by Shinya Yamanaka was done 40 years after the experiments by John B. Gurdon. But, both of their work, try to explain a common question and hence they are awarded the NP together.
Now; Everyone should have heard about Cloning. Remember Dolly?
The foundation for the mammalian cloning experiments were directly based on John B Gurdans work in stem cells. He hypothesized that the genes which regulate pluripotency should be intact even inside the adult cell nucleus. ( genes; which are DNA, are found in the nucleus of cells) So, he conducted a wonderful experiment. He took an egg cell, destroyed its nucleus and “transferred” the nucleus from an adult cell into the egg cell. What it means is, the entire “programming” will now be done by the genes of the adult cells ( as the nucleus of the egg cell now has gene from the adult cell). Surprisingly, a few of the egg cells actually developed, differentiated and became the fully grown organism!!! ( He was experimenting on frogs). So this experiment proved that, even in the adult cells, the genes required for activating pluripotent functionality is intact!!! i.e. the nucleus of a mature cell, retains all the genes required for generating an entire living being.
40 years later, Shinya Yamanaka did an astonishing experiment. He had already identified genes which are vital in the functioning of Pluripotent stem cells. He by then did find around 24 such genes.He hypothesized that, if these genes are transferred into mature cells, then those mature cells can regain its pluripotent power! He introduced all the 24 genes into mature skin cells and interestingly, he found out that, certain skin cells programmed into cells from which the entire cell types can be generated. further experiments showed only 4 out of 24 genes were required for this. he named these cells as Induced Pluripotent stem cells or iPSC. So, the experiment which Shinya Yamanaka did is the “reprogramming” factor here. He re programmed a fully mature adult cell into becoming a pluripotent stem cell. He “induced” this function into these cells and hence called as iPSC.
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