Yesterday was an action packed day. I got to lab early and made a major discovery. Then last night we had an excellent NERD Club meeting. Then as I walked into the front door at 9PM last night, my wife asks me “Did you hear the news?” Sure enough they have been able to make induced pluripotent strem cells (IPS cells) from human cells. Fantastic. As a biologist, I consider the very first and second experiments on mouse cells to be much more important, and the extension of the technique to another mammalian cell as being secondary.
Now a couple of additional points.
1) From initial rumours it seemed that human cells could not be converted to IPS cells with the technique used on mouse cells. We had speculated that this difference may have been due to the fact that it is generally harder for human than mouse cells to become cancerous. Remember that cancer cells and stem cells share many characteristics – they multiply without stopping, and they are dedifferentiated. Why would humans be less predisposed to cancer? Probably with our long life spans, we are much more prone to getting cancer and our cells have many more mechanisms to halt dedifferentiation.
Now in Yamanaka’s paper we are learning that the same four genes that can turn on the dedifferentiating process in mouse cells also works in human cells … so we are not that different after all. But I’ll have to look at the Yamanaka paper to see if anything was changed in the IPS cell generation protocol.
Another point to remember -the 4 gene protocol is still very inefficient. Less than one in a few thousands (and this estimate is low) get converted.
2) It would seem like the magic 4 genes that are needed to convert somatic cells to IPS cells are not absolute. Thomson’s group from the University of Wisconsin (yes, the same guy who first isolated human stem cells), used 2 genes that had been used before (Sox2 and Oct 3/4) but substituted the two oncogenes (myc and klf4) with two other genes (Nanog and lin28). Interestingly, all but one of these molecules are transcription factors, proteins used to turn on other genes. But one of the new guys, lin28, is an RNA binding protein. So it looks like some of the transformative power could lie not only in altering global transcription (DNA => RNA) but also in altering global translation (RNA => protein).
3) This is a major advance not in terms of generating stem cells, but more importantly for understanding how cells take on different fates. We’ve basically discovered how to kick start the program that resets the clock. This reprogramming event seems complicated – it take a couple of weeks to transform normal cells into stem cells – that’s a long time. The reprogramming involves a resetting of epigenetic markers, an activation of certain genetic algorithms that help reprogram the cells, and a turning off of other genetic programs that repress dedifferentitation and cancer. It is a big deal for those who want to understand how cell fate is specified – one of the biggest mysteries in science. Unfortunately all the talk in the media is on how now we can hope to make stem cells for clinical treatments – that day is far away. The major advance here is in our knowledge of biological systems and of (what I like to call) “self-understanding”. Yes we have a further clue into what makes a human body tick, and that is cool in of itself.
4) The fall out. One of the biggest implications of this research is this: the whole idea that a “soul” is created upon conception is not a tenable view anymore. Lets look at the facts – you can take any skin cell, turn on four genes and *presto* you get a cell that can potentially make a new organism, with its own brain, its own mind and its own “soul”. Conception is not required to make a soul. This new person will be one of us and even if he or she has teratomas, he/she will feel, love, hate, cry and laugh just like any other member of our species. It is probable that one day the cells that we created by the activation of four genes will be indistinguishable from the cells from a blastocyst. So how can religious conservatives champion one line of research and not another? How can religious conservatives think that one clump of cells have a soul and the other doesn’t? It just doesn’t add up.
Let me rephrase this … If we can create IPS cells then it means that a “soul” can be created without conception.
Kazutoshi Takahashi, Koji Tanabe, Mari Ohnuki, Megumi Narita, Tomoko Ichisaka, Kiichiro Tomoda, and Shinya Yamanaka
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Cell (07) advance online publication DOI:10.1016/j.cell.2007.11.019 (Yes you can get this paper without a subscription – bravo Cell!)
Junying Yu, Maxim A. Vodyanik, Kim Smuga-Otto, Jessica Antosiewicz-Bourget, Jennifer L Frane, Shulan Tian, Jeff Nie, Gudrun A. Jonsdottir, Victor Ruotti, Ron Stewart, Igor I. Slukvin, James A. Thomson
Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells
Science (07) advance online publication DOI: 10.1126/science.1151526