Transcription and Translation

Blogging on Peer-Reviewed ResearchYesterday 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.

Ref:
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

Comments

  1. #1 Dan
    November 21, 2007

    Nice run-down of the new IPS-cell paper. We’ve known for a while now though that the notion of a literal/non-figurative soul or spirit is the height of absurdity. It’s an article of faith to many however – reason and evidence just don’t measure up to delusions.

    The earlier mouse papers were very interesting though, but this, along with the religious conservative “I told you so” response is rather uninteresting to me. What I can’t wait to see is the use of the IPS cells in regenerative therapy experiments! ;-)

  2. #2 ponderingfool
    November 21, 2007

    4) The implications. 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 pone 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.
    *********************************************

    Which is my big point to all the “bioethicists” who are championing this over using embryos. If they are truly like embryonic stem cells then don’t they have a similar potential to become full fledge human beings? An identical twin is generated by cloning and not conception itself. How is this really any different? If you say one is human life then the other really must also be life as well.

  3. #3 Mr. Gunn
    November 21, 2007

    I’ve heard this argument, and I think it’s weak. They don’t know or care what the cells really are, all they know is “TEH CELLZ COME FROM BABIIEZ!!1!”.

    These cells don’t, so they’re happy. The idea that the two are functionally equivalent only occurs to them after they think, “well, we don’t need to fund ESC research anymore” and “Praise Bush for making this work happen”.

    If you suspend logic and just look at the evidence of their actions, it’s pretty easy to understand where they’re going. The focus, now, is on arguing that ESC research should be stopped entirely because this makes it unnecessary, and then they want to ban any use of eggs in research, then they want to ban any medical procedure done on eggs, then they want to ban contraception.

  4. #4 Nick Anthis
    November 21, 2007

    I agree, Alex. If the iPS cells are virtually totipotent, I’m not sure what ethical issues they really address.

  5. #5 Nella Leung
    November 21, 2007

    I am very surprised the media isn’t picking up on point number 4. They are saying iPS side step the need for embryos, but if they are virtually totipotent, aren’t you CREATING embryos? If iPS can develop into a person, aren’t you are back to square one of the ethical problem?

    How can one type of pluripotent stem cells be said to be a person, yet an induced one not, if they can both develop into a person? Are they saying iPS have no souls so can be experimented on? What if they implanted an iPS into a women, and it grow into a person? Are they going to say that person has no soul? This makes no sense. They fact that scientists are bending backwards to address the nonsensical theology of theists makes me upset.

  6. #6 McDuff
    November 22, 2007

    Abortion opposition, which is what opposition to ESC research springs from, isn’t about the babies, it’s about the restriction of women’s reproductive rights. Therefore, point (4) isn’t an issue because, while it might be creating a potential baby, it’s not inside a woman and so she can’t have her actions restricted to mere incubation chamber. Indeed, any woman who brought an embryo created via this method to term would obviously be doing so by choice.

    The more you look at what gets the anti-choicers up in arms and what they remain oddly silent on, the more you see evidence that it is not and never has been about the babies, and is absolutely about enforcing the White Guys In Charge status quo and turning back the social advances of the latter half of the 20th century.

  7. #7 apalazzo
    November 22, 2007

    McDuff,

    I am just pointing out how their logic (that a “soul” is endowed to matter upon conception) is flawed. Your point regarding their intentions is debatable, and a separate issue.

  8. #8 Acme Scientist
    November 22, 2007

    I got to lab early and made a major discovery. Well???

  9. #9 bayman
    November 22, 2007

    Re #4.
    We don’t know yet if these these IPS can give rise to complete organisms or not. So unless you believe that teratomas have souls, this finding has no more bearing on the origins of the soul than does nuclear transfer cloning (perhaps even less). Although the authors showed sections that demonstrated formation of the various tissues lineages by these teratomas, they did not, to my knowledge, provide any evidence that same teratomas possessed souls.

    Next thing you know, Dubya’s going to ban IPS research because Palazzo said they have souls. And it won’t even be true…

  10. #10 MartinC
    November 23, 2007

    This is going to get the Mormons all worked up. Not only are they busy converting all the deceased souls of the earth to Mormonism, now they have a chance of creating untold numbers of new mormon souls!
    I suppose the answer to this is that to be truly ethical we must ban ALL stem cell research. And prosecute the murderers who have been killing these poor skin cell babies. /sarcasm off)

  11. #11 apalazzo
    November 23, 2007

    Bayman,

    The Jaenisch lab injected IPS cells into tetraploid blastocysts. Since the tetraploid cells can’t differentiate into any body part, the resulting animal must be entirely derived from the injected cells, the tetraploid cells only contributing to the trophoblasts.

    Incidentally, I had a conversation with a good friend who remarked that using the logic of the christian right (that a soul is created upon conception) the tetraploid experiment would indicate that the “soul” would be located in the trophoblasts. These cells do not incorporate into the embryo and eventually die. I guess at some point the trophoblasts must transfer the “soul” to the body? You can see how this line of reasoning can lead you to really bizarre notions. Protect the trophoblasts!???!!!???

The site is currently under maintenance and will be back shortly. New comments have been disabled during this time, please check back soon.