Who’s afraid of stem cells?

The battle over stem cell research has a rich political history – one that revolves around ideals and morals rather than science. Among those most vehemently opposed to embryonic stem cell research are scientific illiterates  such as George W. Bush and conservative religious groups; individuals lacking the knowledge to make an objective decision. But beyond these misguided arguments over federal spending rules, the most important debate is currently taking place within the scientific research machine: Whereas medicine has made incredible advances and cured some impossible diseases using stem cells, not much is known about these notorious cells, and less is known about what we will use them for in the future. 

The history of stem cells is the most twisted drama across all of scientific research.

Since their discovery, stem cells have been the vessel for our hopes of a ‘fountain of youth’. The promise of an imminent cure for all diseases was hyped by Bill Clinton and the politicians who first federally authorized stem cell research in 1993 by providing grant funding for research.

Specifically, this attention was focused on embryonic stem cells – those generated during the first days of pregnancy which are able to grow into each of our roughly 200 different adult cell types. Both scientists and politicians alike thought this omnipotent biological entity could be used to grow new spinal cords for the paralyzed or new hearts for cardiovascular disease patients.

Only 3 years after the first embryonic stem cells were isolated, the shining star of regenerative medicine crashed as fast as it had risen.

The Clinton era had opened a window of federal funding and open guidelines for embryonic stem cell research. This window was shut as restrictions were tightened and funding was withdrawn by the new political right , where ideologies over abortion before science took the center stage in politics.

Ethical concerns were cited for this ban on embryonic stem cell research. Pro-life groups wished to prevent the destruction of any embryo that could potentially become a human life, no matter whether or not they would be discarded into the biological waste-bin. This, in the minds of many scientists, was an unfair restriction. The invention of in vitro fertilization techniques meant that an endless supply of embryonic stem cells could be created without ever involving humans.

While the countless egg cells stored in freezers across the US would never be used to create human life, the pro-life movement was unwilling to compromise on this semantic issue.

These restrictions left researchers with only a few established lineages of embryonic stem cells (the 21 presidential lines) that could be grown in the laboratory. These cultures soon crashed or were contaminated, and hefty restrictions were imposed on access to new lineages.

States such as California tried to take up the slack by providing state-level funding, sometimes to the tune of $3 billion dollars (Proposition 71). But, because of federal restrictions, a red line of tape would be literally traced along the floor, demarcating which equipment could be used for stem cell research. This combination of tightened federal restrictions and a research taboo realistically prevented any progress in the embryonic stem cell field.

Demonstrating that banning embryonic stem cell research was more of a political ploy rather than an ethical concern, unlikely leaders such as Ayatollah Khamenei, Iran’s conservative religious leader, became staunch supporters. To this day, Iran is still at the forefront of embryonic stem cell research.

With the imminent end of embryonic stem cell research in the US and most of Europe, a new source of stem cells was needed for the field of regenerative medicine.

One hope was found in cord blood banking. Stem cells could be obtained from the remnants of birth fluids that may be used to help that baby later in life. To this day, many parents are choosing to save their children’s cord blood, yet the therapeutic applications for those stem cells are not numerous by any standard.

Then, in 2006, a new technology emerged that provided embryonic stem cell opponents with more ammunition. Takahashi and Yamanaka demonstrated that stem cells could be created from normal adult cells. These new cells were named Induced pluripotent stem cells (IPSCs), and were shown to have many of the properties sought by embryonic stem cell researchers. This discovery was awarded the Nobel prize in 2012.

To understand the political and biological ramifications of this discovery, the underlying biology of stem cells needed to be known.

Embryonic stem cells are true stem cells, on their own they are able to generate an entire human body. This ability comes from a combination of biological traits. The most important of these traits is that the DNA of these cells is unmarked (the epigenetic program), and they have an endless regeneration potential. As the stem cells turn into a human body, they journey down an irreversible path called differentiation. Differentiated cells have a limited life span and can only perform limited tasks. Almost all of the cells in the body are differentiated cells, from neurons to heart muscle cells.

Induced pluripotency meant that these differentiated adult cells could be turned back into embryonic-like stem cells. While pro-lifers hailed this discovery as the end to embryonic stem cell research, it was now the turn for the medical community to be afraid of stem cells.

Cancer cells are very much akin to stem cells, and the techniques used to create IPSCs very much resembled the biology of how cancer develops. Researchers had to use well-known oncogenes to reprogram adult cells into stem-like cells.

Since 2006, the technique has been refined to limit the use of oncogenes, but the development of tumors following implantation has remained the greatest obstacle to therapeutic applications.

Because of the promise that induced stem cells offer, any new development in the stem cell field that may be able to work in regenerative medicine has been hailed as a major leap forward and met with much fanfare. Such was the case for the recent acid-induced pluripotency paper. Yet, like many recent break-through discoveries, this paper was retracted, and the authors discredited.

This situation has left researchers with a phenomenal goal to reach for, but a technical impasse that has yet to be overcome.

In the meantime, a 13 year followup after the discovery of embryonic stem cells has discovered that they are both safe and able to cure blindness in patients affected with macular degeneration. While researchers struggle with the safety of pluripotent stem cell induction, scientists have shown that embryonic stem cells are both safe and effective.

So for those hoping to benefit from regenerative medicine in the near future, we have to place our bets on advances from Iran. Fortunately there aren’t any political issues there, right?

Image: Miodrag Stojkovic/Science Photo Library

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