Oct 09 2012

2012 Nobel Prize in Physiology or Medicine

This year’s Nobel Prize in Medicine goes to two researchers whose work was separated by 44 years – both involving the discovery that mature cells could be reprogrammed to become pluripotent cells capable of differentiating into every type of cell in the body.

In 1962 John B. Gurdon replaced the nucleus from a frog embryo with one from a mature intestinal cell. The resulting embryo developed into a normal tadpole. This was a critical proof of concept – it showed that the DNA of a mature specialized cell still contained all the DNA necessary to form every type of cell, and further that this DNA was capable of de-differentiating. This means that whatever process turns a pluripotent stem cell into a mature cell can be reversed. Those genes that are turned off can be turned back on.

Shinya Yamanaka, 44 years later, published a study that showed that this process is far simpler than we previously imagined. By tweaking only four genes he was able to take mature mouse cells and turn them into pluripotent stem cells. His research changed the entire stem cell research debate. Prior to that it was believed that embryonic stem cells were necessary to have fully potent stem cells that could be used in medical research to potentially cure numerous degenerative and other diseases. This controversy led to President Bush’s infamous ban on creating new embryonic stem cell lines.

Suddenly, with Yamanaka’s research, the debate largely faded away. He demonstrated that you could take mature cells and turn back the clock, reverse them into pluripotent cells that behave like embryonic stem cells. This essentially bypassed the core controversy and opened the door for more robust research into possible stem cell therapy.

Yamanaka’s discovery has the further implication that one’s own cells can be used to create genetically identical pluripotent stem cells. This means, theoretically, that skin cells can be taken from a mature patient, they can be turned into stem cells, and then used to grow whatever tissue is needed to treat the patient’s disease. We are, of course, still working on the technology of growing usable tissue. Growing organs is especially challenging, but we have made significant advances in growing hearts and lungs. Already stem cell derived skin cells are being used to treat burn victims.

Developing medical applications will likely take the typical path of new technologies such as this. First there will be amazing hype in the media promising all sorts of miracle cures. Over the next 5-10 years little of this hype with manifest and people will start to ask, “whatever happened to the promised stem cell miracle cures?” The hype will begin to fade, but then over the next 10-20 or even 30 years the promise of this technology will (hopefully) manifest and we will suddenly start to see people getting full organ transplants grown from their own tissue, and stem cell treatments to cure all sorts of horrible diseases.  It’s also possible that the technology will mainly be used in ways not currently conceived, and it will change our life but not how you think.

However it plays out in the future, the ability to reprogram mature cells into stem cells is powerful scientific knowledge. This collective discovery has the potential to give us control over our own biology. It will likely take decades to significantly exploit this knowledge, but there does not seem to be any theoretical limit to the control over biology that this knowledge offers. (Practical limits are another matter.)

I definitely think that the work of Gurdon and Yamanaka is worth a Nobel Prize, and I’m glad that Gurdon has lived long enough to be recognized in this way for his discovery from 44 years ago.

 

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5 responses so far

5 Responses to “2012 Nobel Prize in Physiology or Medicine”

  1. Amy R.on 09 Oct 2012 at 12:09 pm

    Dr. Novella, I disagree with you that induced pluripotent cells (iPSCs) can entirely replace embryonic stem cells (ESCs) at this time.

    1. The reprogramming of iPSCs is a notoriously ineffcient process, with less than 1% of cells used effectively reprogrammed. While this may be acceptable in the laboratory setting, such inefficiency may present difficulties in a clinical application if enough iPSCs cannot be produced to create an adequate amount of cells for differentiation and tissue regeneration.

    2. The use of cMyc in iPSC reprogramming has led to concerns that tumors may arise since cMyc is a proto-oncogene. cMyc can be eliminated from the reprogramming process, but the efficiency is reduced even further.

    3. ESCs and iPSCs, while sharing the ability to differentiate and form embryoid bodies, are not identical at a genetic level. In Takahashi and Yamanaka’s original paper, they noted a great deal of DNA methylation in iPSCs where there was none in ESCs. We do not know the effects of these genetic differences.

    4. At least one research group has found iPSCs did not perform as well in differentiation and tissue formation as ESCs. Mauritz et. al. differentiated mouse iPSCs and ESCs into cardiomyocytes and found iPSCs were less successfully differentiated and produced lower levels of troponin T. Other researchers comparing iPSCs to ESCs have found similar differentiation ability in both, but the Mauritz example shows this is not universal.

    I’m not trying to put down iPSCs. I think they’re neat, and if the problems above are worked out, great. Using iPSCs donated from the patient would eliminate the problem of immune rejection. I just don’t think we’re there yet.

    References:

    Mauritz et. al. “Generation of functional murine cardiac myocytes from induced pluripotent stem cells.”Circulation 2008
    Miura et. al. “Variation in the safety of induced pluripotent stem cell lines“ Nature Biotechnology 2009
    Takahashi K, Yamanaka S. “Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.” Cell. 2006
    Warren et. Al. “Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA.”Cell Stem Cell 2010

  2. Enzoon 09 Oct 2012 at 2:16 pm

    I had the good fortune to attend a lecture by Dr. Yamanaka recounting the tales of his poor graduate student toiling over transcription factor combination after transcription factor combination until something hit. I have no idea how much Shinya was playing to the crowd, but that’s a hell of a path to something that won a Nobel Prize. I found Gurdon’s contribution much more scientifically elegant but LOVE the combination of these two scientists’ work! Congrats to the winners!

  3. Thadiuson 09 Oct 2012 at 3:18 pm

    Cool, but I have read that the “Skin Gun” was a pablicity stunt and not real medicine.

  4. HHCon 10 Oct 2012 at 12:31 am

    Can the skin gun work on third degree burns?

  5. KMorrison 10 Oct 2012 at 2:46 pm

    Researchers at Stanford are currently using iPS cells in hearing loss research. You can read more about the research and Dr. Heller’s vision for iPS cells in hearing loss cures and prevention here: bitly.com/SKmO3I

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