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NO Tampering with Human Life

NO Tampering with Human Life


The scientist credited with developing a new type of stem cell, says he is very concerned about the process. The ethical problems go far beyond any issues with embryonic stem cells.

For a decade, medical research laboratories around the world have investigated the potential of embryonic stem cells. That is in spite of the profound ethical issues involved with these cultures. For a start, the work involves ripping apart developing human embryos (individuals a few days old) in order to extract the stem cells, and secondly because women must donate eggs, an uncomfortable and dangerous process, in order for suitable embryos to be created.

The attraction of embryonic stem cells is that they have the potential to develop into any, or all, of the cell types found in the human body. ‘Pluripotent’, is another term for this potential of embryonic stem cells to differentiate into many, or all, of the various types of cell in a fully developed individual. The word pluripotent comes from the Latin plures, meaning ‘very many’ and potens, meaning ‘powerful’.  Because the term pluripotent carries less emotional baggage than the term embryonic, in that fewer people know the meaning, American scientists have shown a preference for the term pluripotent when referring to cultures derived from embryos. It is evident therefore that many people would be pleased if similar results to embryonic stem cell cultures could be obtained by some other means.

In 2006 Shinya Yamanaka and Kazutoshi Takahashi of Kyoto University in Japan began to work on cultures of adult mouse skin cells. By means of retroviruses, four genes were added to the culture and some cells ended up with all four genes inside them. A retrovirus is backwards in its action. It is able to insert its genetic material into the DNA (genetic information) of the host cell. Thus in some cells, all four genes now were inserted into the mouse genetic information.

The four genes, called Oct4, Sox2, Kfl4 and Myc, code for proteins which cause other important genes to be expressed. The resulting cascade of expression by other genes , each calling for their own protein to be produced, in this case leads to the skin cells becoming pluripotent. Neither eggs nor embryos were needed to produce these pluripotent mouse cells. The Japanese then termed their new cultures ‘induced pluripotent stem’ cells or iPS cells, for short.

The interesting thing about this new technique is that it is relatively easy compared to the difficulties of working with eggs and embryos, and, what is more, it is not subject to any licensing requirements from boards concerned with ethics. At this point however the research involved only mice.

On the down side, the success rate was low. At any one time, less than 0.1% of the skin cells were successfully converted to the pluripotent state. In addition, some other disquieting facts were evident. The iPS cells are riddled with viruses. Some of these viruses have the potential to activate oncogenes (able to turn a normal cell into a cancerous one). In addition, one of the inserted genes, Myc, has also been implicated in the onset of cancer.

When the pluripotent cells were added to developing mouse embryos, the iPS cells developed too and became part of the baby mouse. That individual could now be called a chimaera or composite creature, with a combination of tissues derived from very different sources. Interestingly, 20% of the baby chimaeric mice developed cancer.

On November 20, 2007 Dr. Yamanaka announced that he had used his retrovirus technique to produce iPS cells in a culture of human skin cells. Again, the success rate was very low, only 10 successful cultures from 50,000 skin cells. The announcement caused some experts to renounce other techniques which involve use of human eggs. Iam Wilmut, famous as one of the creators of Dolly, the cloned sheep, announced that he now plans to use Yamanaka’s technique in his research.

On the premise that it is hard to argue with success, the Japanese government rushed to develop a Japanese based centre for iPS research. Also, by December 22, only one month after the initial announcement, the science ministry announced plans to increase funding tenfold for iPS research in Japan.

This sudden action on the part of the Japanese government, is very rare. However they did not want to lose the initiative in this popular field of medical research. After all, the benefits of the research are attractive to many people. The technique could enable patient-specific stem cells to be produced. Some day, it is hoped, the cultures may be safe enough (not cancer inducing) to use in the patients from whom the cultures were derived. Such patients could be provided with healthy heart cells, nerve cells, insulin producing cells or whatever the patient needs to return them to a healthy state.

It all sounds like a win/win situation. Dr. Yamanka however soon declared that the ethical issues with iPS cultures are worse than they are with embryonic stem cells. For a start, since the technique is relatively easy, laboratories all over the world could soon be producing such cultures, all without any ethical oversight at all. Dr. Yamanka is greatly concerned that some scientists will try to produce human gametes (sex cells) from the cultures. It may not be too difficult to produce both eggs and sperm from a culture of cells from a man. Thus a child could be conceived from male parents alone. This would not work on cells from a woman, however, since these cells lack a Y chromosome, essential for the formation of sperm. Dr. Yamanaka also fears that maverick scientists, working with iPS cells, may try to clone a human. Such techniques are already being attempted with mice.

As a result of Dr. Yamanaka’s concerns, on Feb. 21, 2008, the Japanese government sent directives to all research agencies. In Japan, no one is to attempt to implant embryos made from iPS cells into human or animal wombs, to produce an individual in any way from iPS cells or to introduce iPS cells into any stage of developing embryo or unborn young. Also the production from iPS cells of cells which lead to gametes is expressly forbidden.

Dr. Yamanaka, burdened by the possible ramifications from his research, encouraged the Japanese government to insist upon important controls on Japanese research using iPS cells. What, one wonders, are similar labs in other parts of the world undertaking at this time? Will other governments issue similar directives? We hope so, and soon. It can?t hurt to make sure that governmental funding agencies are informed about these issues.

Margaret Helder
June 2008

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