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. ┬áIt’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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