The Epigenetics Revolution

The obvious thing of course would be for someone to repeat Yamanaka’s work and see if they could get the same results. It may seem odd to people working outside science, but there wasn’t an avalanche of labs that wanted to do this. It had taken Shinya Yamanaka and Kazutoshi Takahashi two years to run their experiments, which were time-consuming and required meticulous control of all stages. Labs would also be heavily committed to their existing programmes of research and didn’t necessarily want to be diverted. Additionally, the organisations that fund researchers to carry out specific programmes of work are apt to look a bit askance if a lab head suddenly abandons a programme of agreed research to do something entirely different. This would be particularly damaging if the end result was a load of negative data. Effectively, that meant that only an exceptionally well-funded lab, with the best equipment and a very self-confident head, would even think of ‘wasting time’ repeating someone else’s experiments.

Rudolf Jaenisch from The Whitehead Institute in Boston is a colossus in the field of creating genetically engineered animals. Originally from Germany, he has worked in the USA for almost the last 30 years. With curly grey hair and a frankly impressive moustache, he is immediately recognisable at conferences. It was perhaps unsurprising that he was the scientist who took the risk of diverting some of the work in his lab to see if Shinya Yamanaka really had achieved the seemingly impossible. After all, Rudolf Jaenisch is on record stating that, ‘I have done many high risk projects through the years, but I believe that if you have an exciting idea, you must live with the chance of failure and pursue the experiment.’

At a conference in Colorado in April 2007 Professor Jaenisch stood up to give his presentation and announced that he had repeated Yamanaka’s experiments. They worked. Yamanaka was right. You could make iPS cells by introducing just four genes into a differentiated cell. The effect on the audience was dramatic. The atmosphere was like one of those great moments in old movies where the jury delivers its verdict and all the hacks dash off to call the editor.

Rudolf Jaenisch was gracious – he freely conceded that he had carried out the experiments because he just knew that Yamanaka couldn’t be right. The field went crazy after that. First, the really big labs involved in stem cell research started using Yamanaka’s technique, refining and improving it so it worked more efficiently. Within a couple of years even labs that had never cultured a single ES cell were generating iPS cells from tissues and donors they were interested in. Papers on iPS cells are now published every week of the year. The technique has been adapted for direct conversion of human fibroblasts into human neuronal cells without having to create iPS cells first[11]. This is equivalent to rolling a ball halfway up Waddington’s epigenetic landscape and then back down into a different trough.

It’s hard not to wonder if it was frustrating for Shinya Yamanaka that nobody else seemed to take up his work until the American laboratory showed that he was right. He shared the 2009 Lasker Prize with John Gurdon so maybe he’s not really all that concerned. His reputation is now assured.

Follow the money

If all we read is the scientific literature, then the narrative for this story is quite inspiring and fairly straightforward. But there’s another source of information, and that’s the patent landscape, which typically doesn’t emerge from the mist until some time after the papers in the peer-reviewed journals. Once the patent applications in this field started appearing, a somewhat more complicated tale began to unfold. It takes a while for this to happen, because patents remain confidential for the first year to eighteen months after they are submitted to the patent offices. This is to protect the interests of the inventors, as this period of grace gives them time to get on with work on confidential areas without declaring to the world what they’ve invented. The important thing to realise is that both Yamanaka and Jaenisch have filed patents on their research into controlling cell fate. Both of these patent applications have been granted and it is likely that cases will go to court to test who can really get protection for what. And the odd thing, given that Yamanaka published first, is the fact that Jaenisch filed a patent on this field before him.