The Epigenetics Revolution

How could that be? It’s partly because a patent application can be quite speculative. The applicant doesn’t have to have proof of every single thing that they claim. They can use the grace period to try to obtain some proof to support their assertions from the original claim. In US legal terms Shinya Yamanaka’s patent dates from 13 December 2005 and covers the work described a few paragraphs ago – how to take a somatic cell and use the four factors – Oct4, Sox2, Klf4 and c-Myc – to turn it into a pluripotent cell. Rudolf Jaenisch’s patent potentially could have a legal first date of 26 November 2003. It contains a number of technical aspects and it makes claims around expressing a pluripotency gene in a somatic cell. One of the genes it suggests is Oct4. Oct4 had been known for some time to be vital for the pluripotent state, after all, that’s one of the reasons why Yamanaka had included it in his original reprogramming experiments. The legal arguments around these patents are likely to run and run.

But why did these labs, run by fabulous and highly creative scientists, file these patents in the first place? Theoretically, a patent allows the holder access to an exclusive means of doing something. However, in academic circles nobody ever tries to stop an academic scientist in another lab from running a basic science experiment. What the patent is really for is to make sure that the original inventor makes money out of their good idea, instead of other people cashing in on their inventiveness.

The most profitable patents of all in biology tend to be things that can be used to treat disease in people, or that help researchers to develop new treatments faster. And that’s why there is going to be such a battle over the Jaenisch and Yamanaka patents. The courts may decide that every time someone makes iPS cells, money will have to be paid to the researchers and institutions who own the original ideas. If companies sell iPS cells that they make, and have to give a percentage of the income back to the patent holders, the potential returns could be substantial. It’s worth looking at why these cells are viewed as potentially so valuable in monetary terms.

Let’s take just one disease, type 1 diabetes. This typically starts in childhood when certain cells in the pancreas (the delightfully named beta cells in the Islets of Langerhans) are destroyed through processes that aren’t yet clear. Once lost, these cells never grow back and as a consequence the patient is no longer able to produce the hormone insulin. Without insulin it’s impossible to control blood sugar levels and the consequences of this are potentially catastrophic. Until we found ways of extracting insulin from pigs and administering it to patients, children and young adults routinely died as a result of diabetes. Even now, when we can administer insulin relatively easily (normally an artificially synthesised human form), there are a lot of drawbacks. Patients have to monitor their blood sugar levels multiple times a day and alter their insulin dose and food intake to try and stay within certain boundaries. It’s hard to do this consistently over many years, especially for a teenager. How many adolescents are motivated by things that might go wrong when they are 40? Long-term type 1 diabetics are prone to a vast range of complications, including loss of vision, poor circulation that can lead to amputations, and kidney disease.

It would be great if, instead of injecting insulin every day, diabetics could just receive new beta cells. The patient could then produce their own insulin once more. The body’s own internal mechanisms are usually really good at controlling blood sugar levels so most of the complications would probably be avoided. The problem is that there are no cells in the body that are able to create beta cells (they are at the bottom of one of Waddington’s troughs) so we would need to use either a pancreas transplant or perhaps change some human ES cells into beta cells and put those into the patient.

There are two big problems in doing this. The first is that donor materials (either ES cells or a whole pancreas) are in short supply so there’s nowhere near enough to supply all the diabetics. But even if there were enough, there’s still the problem that they won’t be the same as the patient’s tissues. The patient’s immune system will recognise them as foreign and try to reject them. The person might be able to come off insulin but would probably need to be on immuno-suppressive drugs all their life. This is not really that much of a trade-off, as these drugs have a range of pretty awful side-effects.