Induced Pluripotent Stem Cells: The End of the Ethical Debate

Today, two truly momentous papers were published in Science and Cell, respectively. These papers were so important that even Yahoo! News recognized their importance, and news services prefer stories about giant bugs.

These “induced pluripotent stem cells” (or iPS, as opposed to embryonic stem cells, or ES) produced by these two labs are important for a variety of reasons.

First, these cells completely end the whole debate about whether or not obtaining stem cells from the destruction of a human embryo is ethical. That’s it. It’s over. Don’t want to hear any more about it.

Assuming these cells are indeed truly pluripotent, and there is every indication they are, and if none of the caveats below are a problem, then this is it. In the papers above, researchers used several different types of human cells, ones from an adult woman’s face (a 36-year-old Caucasian woman, in Takahashi, et al,) and foreskin fibroblasts (Yu, et al,), which are cells harvested during the circumcision of newborn boys.

(You didn’t think we just threw those cells away, did you? They’re essentially fetal cells, a veritable cell culture gold mine. They’re used for many kinds of research, especially growing viruses in culture. Plus, if you grow enough of them and sew them into a wallet, and then rub the wallet, it turns into a suitcase. Sorry, old joke.)

Second, there was an additional ethical problem with ES cells, though it was considered secondary to the destruction of human life issue. To obtain human ova to perform nuclear transfer and thus produce ES cells, a woman had to undergo hormone therapy and surgery. Granted, the procedures are pretty much the same as in IVF, but ovulation-inducing fertility drugs have been linked with later ovarian cancer.

Another concern is that human ova would be come very valuable as a cure for everything from spinal cord injuries to Parkinson’s to Alzheimer’s to genetic diseases, etc. Should you pay women for this valuable resource and to chance getting ovarian cancer at a later time?

Again, these debates are now ended. These iPS cells don’t need eggs.

Third, using cells from an adult woman’s face to produce iPS cells is truly a breakthrough. This provides the proof-of-concept that an adult’s cells can be reprogrammed to pluripotency. If only fetal cells or newborn cells were possible to reprogram, this technique would be useful to correct birth defects or inborn genetic diseases but could not help diseases like Parkinson’s or cure spinal cord injuries.

Fourth, this lentivirus technique is easy. Really easy. Many, many labs use the lentivirus vectors and selection techniques described in these papers to produce stably transfected cell lines. I’ve done it. When this technique is refined and, hopefully, declared safe, labs all over the country could begin using this protocol for patients.

Nuclear transfer (the “Dolly” technique) that uses ES cells, on the other hand, is much more difficult.

There are, as always, some caveats. This technique will probably produce stem cells suitable for many kinds of research. It’s going to be a huge boon to labs.

It may not safely work for people. The four genes used are transcription factors, and their upregulation (which means when more is produced) is associated with cancer cells. Cells produced using this technique may cause cancer instead of cures. Takahashi, et al, used Oct3/4, Sox2, Klf4, and c-Myc. (As a virologist, seeing Myc in there gives me the proverbial willies, even if it is the c-Myc gene and not v-Myc.) Yu, et al, used Oct4, Sox2, Nanog, and Lin28, though Lin28 may not be necessary.

“Lentiviruses” are retroviruses. The retroviruses used to insert the four genes into the cells may damage the cells’ DNA when they integrate into the chromosomes and thus cause cancer.

Yet, the possibility of a cure may outweigh the possibility of future cancer. Women choose the increased risk of future cancer to have children by ovulation induction, and they do it often.

Think of it this way: if you had a profoundly dehabilitating disease, such as Parkinson’s, or early-onset Alzheimer’s, or a spinal cord injury, you might be given the choice between a cure (or a profound reduction in symptoms,) but the risk might be a 10% chance of cancer in the next decade.

Wouldn’t you want the choice?

TK Kenyon, author of RABID: A Novel and CALLOUS: A Novel (Apr 2008)

RABID is “[A] philosophical battle between science and religion ... with four very subtle and intriguing central characters. This is a novel quite unlike most standard commercial fare, a genre-bending story--part thriller, part literary slapdown with dialogue as the weapon of choice.” –Booklist Starred Review

Read “Why Dante Became A Priest: Communion Is A Kiss,” the prequel to RABID! You can even read it on your Amazon Kindle!