I’ve hit this issue before. But it’s in the news again, so I thought I’d return to it. For a little background, you can see a piece I wrote or a highly recommended, if slightly older article written by a real doctor. Sorry for the lack of links. I’ll throw up a link list sometime in the next few days.

When Michael Reagan stood up at his father’s funeral and cried about how Embryonic Stem Cells could have saved the man who ended the cold war, I cried a little myself. I cried because I wish I was old enough to have better memories of a president who was by most accounts an amazing statesman and just a great man all around. I cried because it was wrong for the man’s own flesh and blood to use his father’s death as an excuse for political posturing. But mostly I cried because every time someone stumps for the new panacea, I see development of a real cure farther and farther away.

I’ll start by saying that my political position is that despite being pro-life, I have no moral qualms with harvesting new ESC cultures from cord blood or discarded embryos. In the former case, there is simply no moral quandary; the cells weren’t taken from an embryo/fetus/bay. With regard to the latter case, the operative term here is discarded. Any objections one would have to harvesting stem cells in that case would also apply to organ donation in adults as far as I’m concerned.

My scientific position is that ESC’s make for excellent models but bad therapy. ASC’s on the other hand are the exact opposite. Each have their place in the biomedical sciences and medicine. Embryonic stem cells are comparatively easy to harvest, sustain, and grow in culture. They’re also capable of differentiating into more kinds of tissue than any given adult stem cell. In addition, ESC lineages are standardized (currently 19 of them. Should be more), meaning studies are more repeatable. Adult stem cells, on the other hand are not as amenable to laboratory manipulation. They’re harder to get to (although we’re finding more accessible places where they exist), they’re harder to sustain, and they’re much harder to grow in cell cultures. On the other hand, despite tiny budgets and little attention from funding bodies or the public at large, ASC researchers have had much more success in therapeutic applications in animal models and humans alike. Even at a theoretical, freshman biology level, the advantages of ASCs in therapy are fairly obvious.

Embryonic Stem Cells

A recent issue of Scientific American highlighted the similarities between ESC’s and cancer cells (which is one of the objections to the use of ESC’s as therapy). ESC research may lead to greater understanding of the etiology (development) of various cancers. And more importantly, since when we were embryos our stem cells didn’t go tumor on us, we may be able to reverse engineer the process by which ESC’s are controlled. This could very well lead to better cures and preventive treatments when it comes to cancer. ESC’s are also a good deal more pliable than ASC’s (another problem when it comes to therapy). Which means you can do more with them in a laboratory setting, particularly when it comes to understanding developmental biology. ESC’s give us a convenient model with which to study proliferation, differentiation, and apoptosis. They’d be useful in studying how things go wrong in human embryonic development as well as how things go right. As well as in understanding the nature of the switches that turn these cells on and off and how to operate them. This is stuff we’ve been doing for decades, but thus far only with animal embryos. The moral implications of raising a human embryo for the purpose of experimentation are pretty grim. ESC harvesting methods are much more morally neutral while allowing many of the same benefits.

Of course, what makes ESCs so suited as models is what makes them so poor at therapy. Which is something the ESC researchers conveniently forget to tell the press and the public. After high school, I worked in a cell biology lab with CHO cell cultures. CHO stands for Chinese Hamster Ovary. No ordinary reproductive cells, these are all descended from an unlucky rodent’s bout with cancer. I always found it interesting that what made it such a useful laboratory model is why it killed that poor little pet. Like cancer, ESCs are immortal. Like cancer, a lot of the regular processes that differentiated cells go through are shut down. Like cancer, ESCs love to grow. Getting an ESC to stop growing once it’s in an adult body has proven to be a difficult proposition in animal models. Getting an ESC to turn into the kind of cell you want is also tough. And assuming you’ve got past all those roadblocks, you now have to deal with immunocompatability issues. When you get an organ transplant there is a pretty high risk of rejection, no matter how close a match the new organ is. It isn’t you. Your immune system knows it isn’t you. And it wants to kill it off. The immune system is a marvelous and sophisticated system that was designed for the sole purpose of killing off foreign cells. If you want those donor cells, tissues, or organs to stick around, you have to cage up that immune system, leaving yourself open to the depredation of other foreign cells. In other words, taking immunosuppresants for the rest of your life is not exactly fun. ESC researchers don’t mention to you that these problems apply to ESC therapy as well, do they? The one big success I’ve seen with them is in the nervous system. Which is somewhat expected. The nervous system is one step removed from a lot of other bodily processes, including circulatory and immune processes. Not to mention the fact that glia (support cells in the brain and nerves) secrete a chemical that actively inhibits nerve cell division and proliferation, meaning less likelihood of tumors. The one big benefit to ESCs compared to ASCs is that because they are less constrained, a single ESC culture can be turned into many different types of tissues, whereas any given ASC colony is significantly more limited.

Adult Stem Cells

What about adult stem cells, surely they can’t be any better, right? Not as models, no. ASCs are by their very nature dormant. That’s part of why they’re so hard to find and why people weren’t even sure they existed until recently. They’re hard to culture and hard to ‘turn on’. And because ASCs are at a later stage of differentiation than ESCs, they can turn into fewer types of cells. Meaning that it might take 2 or 3 different ASC colonies taken from different parts of the body to create all the kinds of tissue you can with just one ESC colony. ASCs can also be rather hard to get to: the hollows of your bones, deep in your brain, embedded in your heart muscle. Not a whole lot of people are going to volunteer for major operations just so some guy with no social skills in a white coat can play with test tubes. And, even if you could get people to do that, you’d still have the problem of lack of standardization. A researcher using stem cells he harvested from my bone marrow could do one experiment and get completely different results from another researcher halfway around the country who used your stem cells, not because the experimental process is unpredictable, but simply because you and I are different, and so are our cells.

Again, these weaknesses as a model translate to strengths as therapy. Imagine that you are told you have to hold a gun to the head of your best friend and you have your choice of two trigger types. One gun doesn’t go bang as long as you pull the trigger. Release it and you’ll be covered in brain stew. The other gun is much more conventional. If ESCs are the former, ASC’s are the latter. I’m pretty sure which one I would choose. While ASCs can be hard to get to, more accessible sources (that don’t require surgery) are being found even as we speak. These same studies are also finding that ASCs are easier to culture and are perhaps more flexible than was once imagined. At any rate, a situation in which one person has multiple degenerative disorders each needing a different ASC is bound to be rather rare. And the implications of self-harvesting for therapy are pretty obvious. Unlike ESCs–which are essentially transplants–ASCs are you. They’re your DNA and your tissue. Instead of organ transplantation, the process is more analagous to a scar fading to nothing over time.

Conclusion

Both ESCs and ASCs have much to offer us in understanding and treating disease, and they do so in a complementary, rather than competitive manner. Of course, research is highly competitive, and so whichever works better in a laboratory setting is the more likely to be funded. And it’s true that ESCs have greater potential to increase our understanding of cell biology because of this. But treatment doesn’t necessarily require understanding. When Fleming invented Penicillin he had no idea that the compound contained within put holes in bacteria cell walls, causing them to burst open. He just knew that the stuff killed bacteria. When Edward Jenner invented the smallpox vaccine, he probably had very little idea of how immune systems worked, he just knew that if you gave someone cowpox (which isn’t deadly) they woudln’t get smallpox (which is). Understanding can improve treatment, which is why it’s important. But there’s no harm in getting the ball rolling, which is exactly what we’re refusing to do by focusing on the politically expedient and the glamorous (if laboratory biology can be glamorous).

Adult stem cells offer us the potential to literally heal ourselves. To quote some old dead guy, ’tis a consummation devoutly to be wished’