Many of us will have rejoiced at the award of a Nobel Prize to Sir John Gurdon (shared with Shinya Yamanaka) for his work leading to the therapeutic use of human stem cells. It’s not every day that a pupil whose scientific ambitions were described as quite ridiculous by his teacher can prove the prophecy magnificently wrong. He challenged the dogma that the specialised cell is irreversibly committed to its fate and demonstrated his claim by producing a tadpole within a frog’s egg, using a transfer of nuclear DNA.
That was in 1962. More than 40 years later the question of whether mature cells could be re-programmed back to pluripotent stem cells (immature cells that are able to develop into any of the 220 cell types in the body) was answered by Yamanaka in 2006, through the introduction into the cell of a few specific genes.
Apart from the promise of a far better understanding of the relationship between cells and disease, and the development of potential cures, we note that these discoveries might make it unnecessary to continue with embryonic stem-cell research, with its corresponding ethical problems.
In looking at this issue we should first be aware that this whole field is really very new. Currently there are no less than 477 studies, reported internationally, involving stem-cell research. The knowledge bank changes literally from day to day. Nevertheless. we can begin to make sense of it all by looking at the broad principles.
One of the marvels of genetics is that the identical stem cells of an embryo are programmed so that they can develop into all the specialised cells of the human body. Gurdon came to believe that each cell had the potential to turn back this development so that it was restored to its original state. The prospect was a kind of Holy Grail through which damaged and diseased human organs could be re-grown. In later years it came to be thought that the obvious, and immediate, source of such pluripotent cells was the embryo, using either a “spare” embryo from in vitro fertilisation or one bred for the purpose. Unsurprisingly it was pointed out that the dignity and rights of human beings from conception onwards were being violated. But those scientists, for whom the end justified the means, continued notwithstanding. In practice it appears that few, if any, cures have resulted from this research. GeronCorp, the world’s leading embryo research company, announced, in November 2011, that it was closing down its stem cell programme and concentrating elsewhere.
By contrast, adult stem-cell research has made considerable progress, for example in the treatment of heart damage. But here, too, we are still making infant steps. These stem cells offer the possibility of the re-building of organs and the treatment of many diseases and disabilities such as Parkinson’s disease, amyotrophic lateral sclerosis, spinal cord injury, burns, heart disease, diabetes, and arthritis. They have been known for a long time, and are to be discovered in a large number of different tissues. They appear to act as a kind of reserve, coming into action when the tissue concerned requires healing. They can be collected and artificially infused into the right tissue or organ to bring about growth. Their use in organs other than their native tissue appears to be very limited, and in order to obtain “universal” stem cells, re-programming is required. This is where we came in.
Enter Shinya Yamanaka. He experimented by using retroviruses (a type of virus which can transfer genetic code to its host) to transcribe different re-programming genes into the DNA of an ordinary adult cell – until he found the four which did the trick. The induced pluripotent stem (iPS) cell was ready to be returned to its host. There was, however, a problem. The retrovirus itself proved capable of causing cancerous changes, and so other methods of transcription have had to be used. Work in refining and developing technologies continues.
The advantages of iPS cells are considerable. Ordinary body cells provide the source material and, when that source can be the patient awaiting treatment, rejection by the immune system is unlikely. Not only may they have major therapeutic and reconstructive purposes, they provide material on which drugs intended for human use can be tested and the nature of diseases better understood. There is even experimental work being done on using the technique to alter rogue genes.
Yamanaka was able to report that human iPS cells were identical to stem cells in all relevant ways. But life is not so simple. As other laboratories reproduced and extended his work, various hitches have materialised. None of these have proved game-changers, but they remind us that we are talking about years, rather than months, of painstaking work before we will know and really benefit from this development.
Does the advent of iPS cells spell the end of that ugly embryonic stem-cell work, which involves the death of so many young? I suspect not – at any rate for the time being. It can always be argued that more research could produce unique results or that, if the iPS cell programme should stumble for some unforeseen reason, it would be waiting in the wings. In 2009, well after the potential of iPS cells was realised, President Obama reversed Bush’s ban on federal research money for embryonic stem cells. But, in the long run, the money, public or commercial, tends to follow the better bet. Meanwhile, ethicists may like to turn their minds to the theoretical prospect of conceiving humans with sperm and ova developed from skin cells.