Wednesday, 10 October 2012

Good means for good ends: induced pluripotency

Stem cells1

This year’s Nobel prize for medicine1 went to Shinya Yamanaka and John Gurdon for their work on changing adult cells into stem cells, which is a huge deal not only because of the great therapeutic benefits it will hopefully lead to (e.g., repairing heart tissue after a heart attack or reversing the effects of Alzheimer’s) but also because of how that will be achieved. To get a sense of the importance of this work, let’s first take a quick look at stem cells and then give some thought to the relevant ethics behind their use.

There are 230 different types of cells in a human body that compose its various organs, skeleton, nervous system, etc. and that can take a variety of forms and perform a variety of functions (from providing structural rigidity as bones via fighting off bacterial and viral intruders as lymphocytes to secreting hormones such as adrenal gland cells or lining various body cavities such as Boettcher cells). The key here is that there is a tremendous variety of them and that they differ greatly from one another. Looking at the beginning of the development of a human organism – i.e., the embryonic stage, however, shows that it is made up of identical cells at first and that this initial cell type – the stem cell – then differentiates into the great variety seen in the fully formed organism. Realizing that stem cells can develop into any other type of cell has great therapeutic potential, which is already being applied today, e.g., in the case of bone marrow transplants for treating leukemia. The greatest potential seen for stem cells though is to be able to take them and, by genetic engineering, “program” them to become specific other cell types that can then be used to “repair” a patient’s damaged tissues.

Where does one get a good supply of stem cells though? The most obvious answer is: from embryos. During the first 4-5 days after fertilization they consist of around 100 cells that form a sphere-like structure (the blastocyst), whose interior is lined with pluripotent stem cells – stem cells that have the potential to develop into almost any cell type.2 There is a problem here though, that, while the ends are noble - to cure illness, the means are not. An embryo is a human being and even though it just looks like a bunch of cells, it has its unique genetic makeup and potential that make it as a specific human person. Destroying it for the sake of “harvesting” stem cells is taking its life and no amount of arguing that it is done for a good cause undoes that plain fact. Further down the line this attitude also leads to ideas like conceiving a child for the therapeutic benefit of its sick sibling. The despair of a sick child’s parents here is fully understandable and not to be belittled or questioned, but it strikes me as a fundamentally degenerate reason for attempting to bring a new person into existence (for an opinion contrary to mine, see here). In any case, I don’t mean to focus here on attacking the use of embryonic stem cell, but instead to celebrate the discovery of an ethically sound alternative that also has distinct therapeutic benefits.

The discovery in question is a story of two parts. First, Gourdon in 1958 showed (and in 1962 published) that a cell from an adult frog’s intestine contained the full genetic code needed for the whole frog organism. Extracting the genetic information from the adult cell and transferring it into a frog egg resulted in a clone of the original frog. This was a key breakthrough since it showed that cell development is not unidirectional: a mature, differentiated cell nucleus can be made to become immature, undifferentiated. Second, Yamanaka in 2006 showed that it is not only the genetic information that is fully present in differentiated, adult cells, but that these cells can effectively be “reset” back to their stem cell origin. The result are induced pluripotent stem cells (iPSCs) – i.e., differentiated adult cells (e.g., skin) but that were chemically or virally transformed into stem cells and that can then be used therapeutically like embryonic stem cells. iPSCs also have additional therapeutic benefits in that their use would not require immunosuppressants (the cells coming from the same organism that they are later being inserted into) and also that they could be used to test the efficacy of potential treatments before they were given to a patient. In summary, this advance in medicine for which this year’s Nobel prize was awarded will, in the words of Prof Yamanaka, who started his career as a surgeon, “bring […] stem cell technology to the bedside, to patients, to clinic.”

The news of this year’s Nobel prize was wholeheartedly welcomed by the Church, with the European Community’s Bishops’ Conference affirming that it “is an important milestone in recognising the key role that non-embryonic stem cells play in the development of new, medical therapies, [leaving human embryonic stem cell research] ethically-problematic and scientifically and economically less promising.” To my mind the most important aspect of this Nobel prize from the ethical perspective is Prof. Yamanaka’s own experience though. In the scientific, peer-reviewed paper in the prestigious journal Cell, where he and his colleagues published their results, they already indicated that the motivation of their work were “ethical controversies.” In an article in the New York Times, the whole background is then revealed, as Prof. Yamanaka describes the epiphany he experienced while looking down a microscope in a fertility clinic: “When I saw the embryo, I suddenly realized there was such a small difference between it and my daughters. […] I thought, we can’t keep destroying embryos for our research. There must be another way.” To me the most overwhelming message here is that it is not at all as if science and religion were at war,3 but that it is a scientist’s own seeking not only of knowledge but also of goodness that leads to good ends and also to their achievement by good means.

UPDATE (16/10/2012): An article critical of Yamanaka’s work has appeared yesterday that argues that the “reprogramming” of adult stem cells was done based on genetic material originally derived from embryos. While this is certainly a relevant point, I don't believe it changes the gist of my initial take on this work: Yamanaka himself used to work with embryonic stem cells and, following the insight he had about the embryos being similar to his daughters, he started working towards the use of adult stem cells only. Yes, the work he does now would not have been possible without his previous use of embryos (including the fact that he gained insights from them that he now benefits from), and the fact that embryos were destroyed in the past that are now benefiting the adult stem cell method is a loss of human life, but (and there is a but!), taking the view that this latest article does downplays the good means that Yamanaka has developed. Was it good that embryos were destroyed before - no, should it have been avoided - absolutely!, but: is it good that they are not being destroyed anymore - in my opinion, yes. I don’t mean to be too negative about this criticism though, as it is important to have as complete a picture as possible and as the points made do raise important ethical questions. Finally, I have to say I am impressed with the article’s author - Dr. Stacy Trasancos - who in fact followed up suggestions by some of her article’s commenters, who argued that the iPSC approach does not have to rely on human embryonic genetic material and has in fact found that this is likely to be possible. Her objections to the work so far still stand, but there is hope for a method that will not rely on the use of any embryonic material at all. An alternative statement of this position can also be found here.

1 Many thanks to my bestie, BM, who is a medical doctor, for proofreading this post and making sure I didn’t commit factual errors about cell biology that were too gross :).
2 With the exception of the placenta, which requires totipotent cells.
3 Although I do have to admit that such a view is not absent among representatives of either party, as I was sadly reminded by my bestie NP - a bona fide chemist working at Oxford, who recently spoke to a religious audience about the positive relationship between science and religion, only to be faced with a mixture of both positive and skeptical reactions.