In 1998 James Thomson produced the world’s first human stem cell line, which is a single stem cell that is manipulated to divide into new stem cell clones producing a stem cell line. Whilst this opened up a whole new very promising area in genetic research it came under heavy criticism because it required embryonic stem cells. Embryonic stem cells come can only be harvested from a human embryo or a cloned human embryo and in the process the embryo is destroyed. This caused an ethical dilemma for those who considered this to be morally/ethically wrong; unfortunately amongst theirs numbers happened to be Clinton and then Bush. This resulted in an extreme retardation of stem cell research one of the most promising genetic developmental fields since Watson and Crick first put DNA on the map in 1953. To understand why James Thomson’s achievement was and is so important one needs to know why embryonic stem cells are so special and that is contained in the word Pluripotency.
In cell biology a human pluripotent cell has the potential to become any one of the 202 different cells that make up the human body. They are effectively blank cell slates that can be utilised in a wide range of ways and ultimately lead to effective gene therapies for a multitude of ailments. Truly the possibilities are endless and with appropriate research lend the opportunity to treat individuals quite individually, a major step forward from the present throw and let’s see what sticks approach. A big step forward indeed but one that has been effectively neutered so far by misplaced moralistic concerns based primarily in outdated ancient religious values that could never have foreseen the future and the world we live in now. Yet if there’s one thing humankind has proved over and over again where there is a will there is a way. In spite of not because of, genetic scientists have sought a new way around this dilemma and the inevitable funding restrictions that arose from this rather skewed attitude. Enter Shinya Yamanaka of Kyoto University who decided “the best-laid plans of mice and men go oft awry” and that mouse deserved a closer look.
In March 2006 Shinya Yamanaka released the findings of this closer look research in the Cell Journal under the article title, “Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors”. Using mice stem cells Shinya managed to successfully reprogram or induce the embryonic mouse cell cultures into producing the all important pluripotent stem cells. Emboldened Shinya then decided to apply his techniques to human cells, 20 months later his skin deep approach proved most successful.
“Successful reprogramming of differentiated human somatic cells into a pluripotent state would allow creation of patient- and disease-specific stem cells. We previously reported generation of induced pluripotent stem (iPS) cells, capable of germline transmission, from mouse somatic cells by transduction of four defined transcription factors. Here, we demonstrate the generation of iPS cells from adult human dermal fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc. Human iPS cells were similar to human embryonic stem (ES) cells in morphology, proliferation, surface antigens, gene expression, epigenetic status of pluripotent cell-specific genes, and telomerase activity. Furthermore, these cells could differentiate into cell types of the three germ layers in vitro and in teratomas. These findings demonstrate that iPS cells can be generated from adult human fibroblasts.” -Takahashi et al., Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined
Factors, Cell (2007), doi:10.1016/j.cell.2007.11.019
Using the techniques Shinya had developed previously for the mice he decided to try and apply them to human Fibroblast cells or skin cells. Harvesting the required cells from a Japanese adult male and female Shinya achieved his inducement by introducing four genes that effectively reprogrammed the original cell into a blank slate pluripotent cell line. Thus in one swoop Shinya has managed to advance stem cell research past the concerns of the moralists and hopefully this will see a major change in worldwide funding. Though it’s not all champagne and streamers yet because of the four genes required for the reprogramming in the inducement process.
One of the genes is a cancer gene that saw a 30% presentation of cancer in the live mice studies as a direct result of its use. This for the moment precludes any immediate human gene therapy solutions but more importantly in light of Shinya’s work it does mean a rather large step forward for stem cell research. James Thomson also undertook a similar independent study that also produced favourable results and is quick to point out; that without the base of embryonic stem cell research that has taken place so far albeit in a limited fashion this new discovery could never have been achieved. He goes on to say in reference to the new cells that although they:
“do not differ from embryonic stem cells in a clinically significant or unexpected way, it is hardly time to discontinue embryonic stem cell research.” – James Thomson
This maybe the case and indeed embryonic stem cells hold the correct blueprint for pluripotent cells that needs to be constantly referred to in further research. But one of the distinct advantages of induced pluripotent skin cells is that they are truly blank more so than embryonic stem cells. This means that they are more neutral and can be used for any person irrespective of a donor matching type of situation that is necessary for embryonic stem cells at the moment.
Whichever way you look at it Shinya and James have given the field of stem cell research a giant leap forward. One that after 10 years since James’s breakthrough and the tortuously under funded slow progress since, is like a ray of light in the darkness. Perhaps now the morally circumspect investors driven by a overriding minority opinion, (two thirds of the population in the US alone are in favour of human embryonic stem cell research) will finally start putting up the money to move forward in what could be the most important medical research in the history of humanity to date.
