There's a line that politicians opposed to embryonic stem cell research have been peddling lately: recent breakthroughs in stem cell technology have now made ethically questionable embryonic stem cell research obsolete and unnecessary. This isn't a new line - for years, opponents of embryonic stem cell research have always claimed that the latest research (whatever it happens to be) has obviated the need for embryonic stem cells.

Two recent developments have brought this issue back into the public eye. President Obama rescinded Bush's executive order severely limiting federal funding for human embryonic stem cell research. And recently, in a Nobel-caliber breakthrough, scientists have learned how to reprogram differentiated adult cells into stem cells much like embryonic stem cells. These new cells are called induced pluripotent stem cells, or iPS cells.

So the political line now is that Obama's move was not needed: iPS cells are the breakthrough we've been waiting for; there is no need to work with embryonic stem (ES) cells.

Really?

As amazing as the iPS cell breakthrough is (a Nobel Prize is surely on the way), we still need ES cells. Here's why:

1. ES cells are already closer to real treatments, iPS cells are not. The first clinical trial of a treatment using human ES cells (for spinal cord injury) was approved by the FDA this year. In the case of several other diseases, extensive studies of ES cells in animal disease models have been promising; more clinical trials are looming on the horizon. Should we just drop these studies and wait years until iPS cells possibly catch up?

2. iPS cells have their own unique problems. The technology is still very young - we can't simply substitute iPS cells for ES cells at this point. Let me be clear: I think iPS cells are extremely promising, and eventually we all hope that they prove even better than ES cells. Several challenges need to be overcome first, which include the following

A. Incomplete reprogramming: to make an iPS cells, you reprogram a differentiated (specialized) cell into a stem cell. (ES cells don't need to be reprogrammed to become stem cells - they already are stem cells.) Although iPS cells may look like good stem cells, in many cases the reprogramming may be incomplete. In any treatment where a human patient receives a transplant of iPS cells, we need to be extremely sure of what we're transplanting. Incomplete reprogramming could lead either to ineffective treatments or tumors. The challenge is to develop methods to thoroughly test the state of reprogramming in iPS cells that are destined for human patients.

B. Transgenes: To reprogram a cell into an iPS cell, you insert transgenes into the genome of that cell - foreign genes that will induce reprogramming. These transgenes can have unintended effects, such as the generation of tumors. Recently, in another amazing breakthrough, scientists figured out how to put transgenes in, make iPS cells, and then excise the transgenes after they were no longer needed. This is fantastic, but again, before any iPS cells are put into a human patient, we need to be very, very sure that all transgenes were properly excised. In other words, you don't want to transplant a mix of cells, some of which may have transgenes still hanging around.

C. Transgenes and reprogramming are actually in tension: Transgenes are essentially mutations in the genome, and we want to mess with the genome as little as possible when we make iPS cells for patient use. Thus scientists have tried to make iPS cells with as few transgenes as possible, and they've managed to do it with just one transgene. But the tension is this: the fewer transgenes you use, the less effective your reprogramming may be. So we need to find the right balance: perturb the genome as little as possible, but reprogram effectively.


The bottom line is this: right now, iPS cells are at the stage where they are useful for studying disease and drug response in cells grown in a petri dish, but not for disease treatments. ES cells are at the point where they're being used for treatments in trials. iPS technology has great promise, but it is years behind ES cells. People are being treated with ES cells right now (albeit on a trial basis).

And finally, we can step away from the science and deal with the ethical arguments. I find the ethical arguments against using ES cells dubious, to put politely. It's extreme and downright ridiculous to think that a tiny cluster of a few dozen/few hundred cells has an ethical status equivalent to that of a child or even a fetus.

And in fact, millions of these tiny clusters of cells are destroyed every year - most often through natural, and generally unnoticed, spontaneous abortions. If all of these very early embryos have souls, then God is the most prolific abortionist of them all. Fewer embryos are destroyed in fertility clinics, but still a substantial number, and somehow most people seem OK with in vitro fertilization - you rarely see abortion protesters hanging out around IVF clinics, and nobody's submitting legislation to ban IVF as far as I know.

In other words, the ES cell issue has to be separated from the abortion issue. Aborting a fetus is not the same thing as extracting stem cells from a blastocyst in a petri dish. Those who make the ethical argument against ES cells exactly the same as the one against abortion don't appear to be concerned about being convincing.


Take my ethical argument or leave it, but the science at this point is unambiguous: iPS cells have not rendered ES cells obsolete.