There has been a great deal of public interest in the work of the American Andrew J. French who, together with his colleagues, has succeeded in cloning a human embryo, something the South Korean Hwang claimed to have done two years ago, a claim that was eventually shown to be fraudulent. For Prof. Dr. Christof von Kalle, director of the National Centre for Tumour Diseases in Heidelberg, French’s success is not a ”real scientific milestone” because it was already known from animal experiments that the method actually worked. The judgement of the cancer specialist and stem cell expert: ”For the expert audience this is an interesting finding – associated with methodological improvements.”

Scepticism of the German Research Foundation

In contrast to other research groups, the American team of researchers used the eggs of young women around 20 years old. In addition, speed was of the essence and the researchers carried out somatic cell nuclear transfer (SCNT) as quickly as possible. SCNT involves the removal of nuclei from freshly withdrawn eggs and the replacement of the original nuclei with new ones – in this case the nuclei of male skin cells. However, the team of researchers was unable to achieve their original goal, which was the cultivation of stem cells from cloned embryos. The researchers were hoping that these stem cells would then develop into different somatic cells or even complete organs.

That is one of the reasons why the German Research Foundation (DFG) is sceptical about French’s experiments. For Marco Finetti, the spokesperson of the German DFG, the basic understanding of the cell biological processes in the early development of human cells is not as advanced as to enable the application of SCNT for human therapy. The DFG is also opposed to the fact that the research required the eggs of many young women, eggs that could potentially turn into embryos.

The DFG is hoping for another new but in principle different way of creating stem cells: the reprogramming of somatic cells into a near embryonic state. The DFG regards this as a “state-of-the art, scientifically exciting and most important” possibility. With this aim in mind, the DFG last year launched the “Pluripotency and Cellular Reprogramming” priority programme in the hope of overcoming the dependence on human embryonic stem cells.

Like the DFG, Christof von Kalle is also fascinated by induced pluripotent stem cells (iPS). “This is a completely new quality of cell handling,” said the stem cell expert. Last year, the Japanese Shinya Yamanaka along with German-born Rudolph Jaenisch succeeded in reprogramming the skin cells of mice into an embryo-like state. Ernst-Ludwig Winnacker, the president of the European Research Council in Brussels, believes that this method might become “a real alternative for research and therapy”.

“Since new eggs are produced in every generation, it seemed clear that the principle of a fountain of youth must be anchored in the programme of the cells,” said von Kalle, further explaining that, prior to the intelligent considerations of Yamanaka and his team, it was not known how this programme could be switched on. The scientist from Heidelberg sees Yamanaka’s solution as a “true milestone”. Von Kalle is also confident that it will be possible to switch off the carcinogenic potential that is generally associated with iPS. Both the genes that confer the new programme and the gene shuttles used to introduce these genes into the cells carry this dangerous carcinogenic potential.

Von Kalle is sure that the new technology has a broad potential. In common with many other observers, von Kalle places his highest hopes on the possibility of directly switching on the rejuvenating switches that are present in the genome and switching them off once the cells have been reprogrammed into the embryonic state. This would enable the researchers to avoid the use of gene shuttles that have a carcinogenic potential as well as avoiding the insertion of protooncogenes into the genome. In fact, at this point it becomes clear that the results obtained with the generation of iPS ressemble a valuable coin – to which there is not one but two sides.

The work of Yamanaka and Jaenisch is not only of major importance to stem cell research but also to cancer research. The gene cocktail used by the researchers for producing iPS from skin cells shows – as von Kalle explains – “that many oncogenes are actually stem cell regulation genes”. He is also sure that the scientific findings gained from the further development of iPS will also contribute to a better understanding of the development and progression of cancer. Detailed insights will be available on why cells grow, why they differentiate and how they can be prevented from degenerating. That is why it is not surprising that the Meyenburg Award for outstanding achievements in cancer research was awarded to Shinya Yamanaka in 2007 during a conference held in the German Cancer Research Centre (DKFZ). The award comes with a purse of 50,000 euros, making it one of the most highly prized scientific awards in Germany.

However, von Kalle declines to estimate how long it will take to turn iPS or natural embryonic stem cells into tools that can effectively be used in clinical applications. However, in principle, the stem cell expert is confident: “Since Mother Nature is able to turn embryonic stem cells into a well-functioning organism, I am sure that we will eventually be able to produce organ cells from stem cells in the test tube.”

kb - 10.3.2008
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