The revolutionary work of Nobel Prize winners Sir John Gurdon and Shinya Yamanaka

Last week British scientist Sir John Gurdon and Shinya Yamanaka were awarded the Nobel Prize in Physiology or Medicine 2012 for their ground breaking work in stem cell research.

They discovered that mature cells can be reprogrammed to become pluripotent. The Nobel Assembly said the scientists’ findings have “revolutionised our understanding of how cells and organisms develop and have provided invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies.”

In 1962 Sir John Gurdon made a pivotal discovery that the specialisation of cells is reversible. In an experiment he replaced the immature cell nucleus in an egg cell of a frog with the nucleus from a mature intestinal cell. This modified egg cell developed into a normal tadpole. The DNA of the mature cell still had all the information needed to develop all cells in the frog.
More than 40 years later in 2006 Shinya Yamanaka, who holds academic posts at the Universities of Kyoto and San Francisco, discovered how intact mature cells in mice could be reprogrammed to become immature stem cells. By introducing four transcription factors (Oct4, Sox2, Klf4 and c-Myc) he could reprogram mature cells to become pluripotent stem cells, that is, immature cells that are able to develop into all types of cells in the body.
These induced pluripotent stem cells can be used to study and treat diseases. They can be derived from patients’ skin cells and then differentiated into the affected cell types thus recapitulating the disease in a dish providing a disease model. This enables scientists to identify new drugs to treat particular individuals. For example, this tool allows scientists to understand the abnormal loss of insulin-producing beta cells in patients with diabetes.
Dr Dean Griffiths, a former research scientist at the Gurdon Institute, and Senior Analyst at Cambridge Consultants, commented on the award, stating: “the award is a recognition of the importance of stem cell research in many ways and the fundamental nature of these discoveries have the potential to affect millions of people around the world over coming decades with new medicines being developed for diseases that we were previously unable to identify.”
Sir John Gurdon’s and Dr Yamanaka’s work has proved to be of paramount importance in developing treatments. Together, their work has helped to create an exciting branch of medicine that will offer solutions to the treatment of debilitating diseases. For example, Professor Anthony Hollander and his team at the University of Bristol are using induced pluripotent stem cells to engineer cartilage to treat defects that results from trauma or osteoarthritis. In addition, Dr Robin Ali and his team at UCL Institute of Ophthalmology and Moorfields Eye Hospital are working to use stem cells to restore vision. Induced pluripotent stem cells are also being used as a drug discovery platform by multiple companies, including Pfizer and Roche, to identify drugs that are both safe to use and efficacious.
The UK has maintained a leading international role in regenerative medicine and the UK has the right environment to capitalize on stem cell research with the right support and the excellent work of researchers. This is the second Nobel Prize that the UK has been awarded, in 2007 the Nobel Prize in Physiology or Medicine was awarded to Mario R. Capecchi, Martin J. Evans and Oliver Smithies for their discoveries of ‘principles for introducing specific gene modifications in mice by the use of embryonic stem cells’. Dr Dean Griffiths said “we have an excellent academic research environment and some of the most high profile researchers in the world are operating in the UK”. The UK government has also provided the right legislative environment in which embryonic stem cell research can be performed.
However, to enable this high profile work to continue in the UK Dr Dean Griffiths explains that the government need to do three things. He said: “the government need to provide an infrastructure for scientists to work in to allow communities to develop”. This is already happening, for example, the Welcome Trust and the Medical Research Council are funding a new stem cell research institute in Cambridge. He added: “the government need to support scientific excellence; it needs to support the people who are doing the best science for longer periods of time.” And lastly he added: “we need to attract excellent young researchers and retain researchers and more thought needs to put into better packages to enable researchers to become established.”
He also advised that the vital work conducted by research scientists is imperative to the future of stem cell research. The explained that they need to pursue excellence, be thorough in what they do and try not to rush out their findings.
Although stem cell research still has some way to go it offers exciting possibilities for improving human health. There is a lot of research and clinical trials for cell replacement therapies using cells derived from stem cells that look promising and it is hoped they will come to fruition in the next decade.
Karen Manser
Assistant Editor

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