An important part a scientist’s work is being aware of the ethical issues surrounding their research and the implications these have on the wider community. Some scientists dedicate their careers to resolving these ethical issues. The winners of the 2012 Nobel Prize in Physiology or Medicine, John Gurdon and Shinya Yamanaka, have pioneered a method which hopefully represents a big step towards solving the ethical issues involved in the use of Stem Cells.
The Stem Cell Problem
Imagine that there was a potential cure for illnesses such as Alzheimer’s, heart disease, spinal cord injuries, or any number of others. Then assume that in order to achieve this, an unborn embryo has to be destroyed. What would you do? This dilemma is at the heart of the Stem Cell Problem.
Embryonic Stem Cell’s (ES) are used in a number of areas of research. The use of these cells is controversial since they are taken from human embryos, initially created for In Vitro Fertilisation (IVF) but not implanted, these ‘spare’ embryos are then donated to scientific research. Unfortunately, during the course of the research the embryo is destroyed; a fact which has led some organisations, such as the Catholic Church, to claim that research using ES cells is tantamount to murder.
The reason ES cells are so important to medical research is that certain properties, only possessed by these young cells, makes them ideal for therapeutic manipulations. Mature cells in the human body are highly specialised towards their function, whether this is in the blood, liver, brain or elsewhere. However, stem cells are immature cells which have yet to develop into their final specialised form. When required, the stem cell is stimulated by certain factors in its environment and eventually develops into a specific mature cell type, for example a blood cell. This means that an embryonic stem cell has the potential to become any cell in the body, given the right environment! ES cells are also able to replicate themselves many times over, unlike specialised adult cells. Therefore these cells are invaluable to scientists investigating cell behaviour and methods for regenerating damaged tissue. The therapeutic uses for stem cells range from understanding cancer to regenerating tissue in a whole number of degenerative disorders.
The 2012 Nobel Prize in Physiology and Medicine was recently awarded to two researchers who made extraordinary advances in cell reprogramming. Their pioneering work has given scientists a clearer understanding of how cells function and also provided a method of obtaining stem cells from adult tissue. Thus, potentially solving the ethical issues surrounding the use of ES cells in research.
One of the Nobel Prize recipients is Sir John Gurdon of the University of Cambridge. In 1962, Gurdon transferred a nucleus (the part of the cell which contains DNA) from an adult frog cell into a frog egg cell. The egg developed into a normal tadpole, showing that DNA from a specialised adult cell could be reprogrammed to function in a developing embryo. This was a landmark discovery since, up until this point, it was thought that adult cells “lost” certain components of their DNA so could not function as part of a developing cell. Gurdon’s work showed that this wasn’t the case proving that mature differentiated cells contain a full compliment of DNA; it’s just that some of the DNA in mature cells is inactive. This also showed that mature adult DNA can be reverted to a previous immature form. The work opened the door for many other scientific breakthroughs, including the cloning of Dolly the Sheep in 1996.
Shinya Yamanaka, the second Nobel recipient, built on Gurdon’s work reprogramming mature adult cells back to an immature form. Yamanaka developed a line of cells called induced Pluripotent Stem Cells (iPSCs). He and his colleagues adjusted the expression of certain components within adult cells, enabling them to revert back to their young, stem-cell, form. These reprogrammed cells had similar characteristics to embryonic stem cells, including the ability to mature into a variety of different cell types. Yamanaka then used the same technique with human adult cells, reverting them to a state similar to an ES cell, further developing his concept to be used in the study of human cells and diseases. As they display many of the important properties found in ES cells, iPSCs could potentially be used as a replacement for ES cells, thus eliminating the controversy surrounding the use of embryonic cells in research.
Stem Cells in Organ Transplants
The potential of iPSCs doesn’t stop at replacing ES cells. They could also herald a major advance in the science behind organ transplantation. Since, ES cells can both regenerate themselves several times over and become any cell type, their use in the replacement of damaged tissue is now being studied. Meaning it may soon be possible for patients to receive transplants composed of reprogrammed cells (iPSC’s) from their own bodies. This would solve the major problem of transplant rejection from donated tissues, caused by the recipient’s body recognising the donated organ as foreign. In theory, an iPSC-derived tissue would not be rejected as it would be made from the patient’s own cells.
As a cell biologist, I may be slightly biased, but I think many scientists (especially biologists) would agree that the work undertaken by Gurdon, Yamanaka and their colleagues is incredibly exciting. It represents a great leap forward in our understanding of how cells work and new ways of studying them in a controversy-free environment.
So, does this Nobel prize-winning work signal a solution to the Stem Cell Problem? Alas, no. It is unclear whether iPSCs and ES cells are equivalent on the molecular level, casting doubt on the likelihood of iPSCs being able to completely replace ES cells in research. Another problem, as with many newly discovered techniques, is that the long-term effects of these technologies are unknown. For example, there are concerns that cells derived from any form of stem cells have a tendency to become cancerous. There has also been a surprising report that iPSCs still produce an immune response when transplanted in mice, which would lead to transplant rejection.
So, unfortunately we still don’t have a comprehensive solution to the Stem Cell Problem. However, this does not detract in any way from the discoveries of Gurdon, Yamanaka and their colleagues, and there is no doubt that their innovation, expertise and skills should have been rewarded by the Nobel Prize. Only time will tell just how much more useful their discoveries will be.
Post by: Louise Walker
For more information on the properties and use of stem cells: http://stemcells.nih.gov/