October 9, 2012 | 9
The days leading up to the announcements of the Nobel Prizes as well as the aftermath are gossip heaven for us scientists. We love to speculate who will win and after the announcements, we exchange wild conspiracy theories, talk about the painful snubs and pontificate on whether or not the recipients deserve the honors. Our dark side also tends to chime in and we exhibit some Schadenfreude when the more pompous leaders in a field are snubbed and some of us also salaciously look forward to another Nobel scandal.
The announcement that John Gurdon and Shinya Yamanaka are the recipients of the 2012 Nobel Prize in Physiology or Medicine was a special treat for me. Usually, when I hear about the Physiology or Medicine Nobel Prizes, the discoveries for which the recipients are honored either occurred decades ago or were in areas of biomedical research that are not directly my area of interest.
This year’s Nobel Prize was awarded to Gurdon and Yamanaka for their ground-breaking work, which showed that adult, mature cells can be reprogrammed to an immature, stem cell state. This discovery is the basis of much of the work in my own laboratory and as I write this, I know that stem cells are being cultured in my laboratory using the methods that Yamanaka developed only six years ago. When I read the paper by Takahashi and Yamanaka published in the journal Cell in 2006, I knew that I was witnessing a land-mark discovery by brilliant scientists, and many of us in the stem cell field have been expecting that Yamanaka would receive the Nobel Prize for his work, we just seemed to disagree about the year in which he would receive it.
John Gurdon’s work dates back to the 1950s and 1960s, when he showed that nuclei from adult cells of the Xenopus frog could be transplanted into an enucleated egg and give rise to healthy frogs – the first example of animal cloning. Gurdon challenged the older paradigm that once a cell becomes mature, it cannot go back. His work was a conceptual revolution and many of his colleagues were initially resistant to embracing this paradigm shift. Gurdon’s seminal findings gradually convinced many other scientists to embrace his ideas and he inspired numerous other scientists to attempt cloning of other animals. The mechanisms of how the reprogramming occurred remained a mystery. How could a nucleus of an adult cell suddenly activate the transcriptional program of its embryonic past simply by being transplanted into an egg cell without a nucleus?
This type of nuclear reprogramming was also rather cumbersome, especially in adult mammals. Extracting the nucleus of an adult cell and then injecting it into a single egg cell required a lot of expertise and was not ready for a widespread use in stem cell laboratories. When Yamanaka published a method nearly 50 years later in which the reprogramming to the embryonic-like state could be initiated by merely implanting four genetic regulators into an adult mouse cell, the idea of reprogramming adult cells suddenly caught on. Within a matter of months, other laboratories confirmed the findings and his paper became one of the most highly cited papers in recent history. In a period of just six years, Yamanaka’s paper has been cited more than 4,000 times! Yamanaka then published a second paper in 2007, showing that adult human skin cells could be reprogrammed to the embryonic-like induced pluripotent stem cell (iPSC) state and this has lead to the generation of stem cell lines from numerous patients.
I think most stem cell biologist will agree that both Gurdon and Yamanaka deserve the Nobel Prize for their discoveries. Some may ask why the first author Kazutoshi Takahashi on the landmark 2006 paper was not a co-recipient. Others may wonder about whether the scientists who developed techniques to culture human embryonic stem cells should also have been honored, because without their hard work, Takahashi and Yamanaka may not have been able to culture the human iPSCs. Such questions common after all Nobel Prize announcements, and are in part due to the stringent requirement that the Nobel Prize can be shared by no more than three researchers, a requirement that should perhaps be reconsidered in our age of collaborative and networked discovery.
The question that bothers me, however, is why John Gurdon had to wait so long for his Nobel Prize. He had published many of the papers that convincingly documented successful reprogramming of adult Xenopus cells nearly 50 years ago. This was a pioneering discovery that challenged the paradigm of irreversible differentiation during development and had a major impact on the thinking of not just developmental biologists, but biologists from numerous disciplines.
The Lasker Foundation also recognized the importance of John Gurdon’s work, when it awarded the prestigious Lasker Basic Medical Research Award to both, Gurdon and Yamanaka in 2009. I think the obvious reason for Gurdon’s recognition in recent years is that Yamanaka’s method of reprogramming allowed for a much broader application of Gurdon’s idea to mammalian and human cells, in a manner that can will likely be used for regenerative therapies, disease modeling and screening of patient specific pharmaceutical agents.
If Yamanaka had not published his work on reprogramming mouse and human cells, would Gurdon have still received the Nobel Prize? This is a speculative question, but I think the answer is “No”, because the awarded Nobel Prize is in “Medicine or Physiology“. The title of the prize implies that the discovery has to have a link to medicine or normal physiology, but this makes it difficult to justify awarding the prize for ground-breaking discoveries in biology without a direct relevance for medicine or physiology. When the Nobel prizes were established more than a century ago, biology as an independent science was still in its infancy. The past century has brought us remarkable discoveries in biology, such as those in the areas of evolution or photosynthesis, which do not have a direct medical application. Just like the Nobel Prize in Physics honors great intellectual feats in the field of physics without documenting that these discoveries will lead to new technologies, biological discoveries should be similarly recognized without having to await imminent medical relevance.
Even though Nobel did not establish a Nobel Prize in Economics, the Sveriges Riksbank responded to the recognition for the need of such a Nobel Prize by donating the required money to the Nobel Foundation to establish “The Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel“. It has this convoluted name, because it is technically not a “Nobel Prize” and was not part of Nobel’s will, but it is still administered by the Nobel Foundation like all the other Nobel prizes and this is why in common parlance, we all refer to it as the Nobel Prize in Economics. I think that we have to realize there is a similar need for a Nobel Prize in Biology, to honor outstanding biological discoveries that stand on their own, without having to prove their medical relevance. Establishing the “The Prize in Biology in Memory of Alfred Nobel“, would be one way to recognize discoveries in biology and also foster even greater interest in this field, that will likely become one of the most important sciences of the 21st century.