[Part 1, Intro and Ethics]
[Part 2, Embryonic Stem Cells]
Adult stem cells come in several different varieties. They are already partly set on a path toward some specific tissue. For instance, there are stem cells capable of forming new brain cells, but they cannot form new liver cells, and so on. After we're born, all our stem cells are "adult," except for egg or sperm and their precursors. Even babies have only adult stem cells, except for the sex cells. Therapies based on adult stem cells involves triggering these partially differentiated cells to form their particular mature cell types.
The hard part is finding those adult stem cells to begin with, because they're very rare. Once they're found and tissue cultured, the harder part is getting them to multiply without differentiating until there are enough cells to make a difference. It does you no good to find ten retinal stem cells, painstakingly start culturing them, only to have them turn into proper retinal cells after one division. You have twenty cells after all your trouble, which aren't enough to cure anything.
In an attempt to find richer sources of stem cells, people have been trying other approaches. Umbilical cord blood stem cells are one source which is richer than adult tissue. Since the perinatal immune system is still not fully developed, there are fewer rejection issues than with cells taken from people with fully developed immune systems. Using them in the originating individual, i. e. with no rejection issues, would mean storing the cells frozen under perfect conditions for years or decades, and hoping they still worked when they were needed. Obviously, that's expensive. So, also obviously, there are plenty of companies trying to convince people they need to store cord blood "for your family's health." Cord blood stem cells are partially differentiated blood cells, so their primary use is the same as a bone marrow transplant, i.e. for cancers of the blood, like leukemia, and for other blood disorders. Recent research is also finding ways to differentiate the cells into other tissue types, such as insulin-producing cells. (E.g., breathless news report.)
The ultimate workaround is to cheat. Cells have two main components, nucleus and everything else, called the cytoplasm. The nucleus contains the DNA, and with the usual cognitive predisposition to fixating on hierarchies, we tend to see the DNA as the master program in the cell. In reality, though, the DNA is more analogous to a library. It's the library staff who actually determine how accessible the books are and what's done with them. Those functions are out in the cytoplasm somewhere, and are still very poorly understood. So the easiest way to cheat is to take the nucleus of a cell of interest, and inject that into an egg whose own nucleus has been removed. This is called somatic cell nuclear transfer (SCNT), i.e. transfer of the nucleus of an ordinary body cell, or "somatic" cell. The egg cytoplasm has the ability to make all the DNA in the nucleus accessible again, and to read off any part of it, and therefore theoretically to make any cell type or organ desired.
Or, theoretically, SCNT can make a whole new human being. This is the human cloning you hear about now and again. It's worked in mice and, famously, sheep. However, "worked" in this case means "shown to be feasible," not "worked just like normal development." Some 30% of naturally produced zygotes (fertilized egg+sperm) result in births, most of them developmentally normal. In cloned mice, the success rate is between 2%-15%. In cloned sheep, it's less than 1%. From a human cloning perspective, the most difficult question is not the high failure rate, but what to do with all the abnormal births. Those are much commoner than normal ones (more on that in a bit), unlike the natural system. So a cloned animal could be born with, say, underdeveloped lungs. If it's a sheep, it's put out of its misery when the researchers realize it won't survive. What would you do in that case with a human clone?
Development in clones is often abnormal because the gene regulation involved is mindbogglingly complicated. In natural development, egg and sperm have the correct "imprint" on their DNA. Think of the imprinting as little tags flagging the important books in the DNA library. The tags are in all the right places to go through the complicated process of embryonic development. As the cells mature, it's essential to move the tags around. Whole sets of genes are tagged "Do Not Use." Never, for instance, make another arm again. In cloning, all those tags have to be rearranged back to the pre-embryonic state before anything can be done. Furthermore, DNA derived from sperm is tagged differently from that of eggs, and the contribution of that tagging is subtle but is increasingly recognized as important. The egg's "librarians" do their best, but too often the task seems to be too big to handle.
Cloned cells also show too much variation in telomere length, which is another cell development issue, and which may indicate long term problems with the health of the resulting clone. Because of the large differences between species in clonability, it won't be possible to know the implications for humans until there's a large sample size of great ape clones. At present there are none.
Cloning of humans and great apes (collectively called primates) hasn't reached even a sheepish level of success. People aren't sure why yet, but there is some evidence that the way the cell aligns chromosomes during cell division operates within even narrower parameters in primates than other animals. (For the scientists among you, “primate NT (nuclear transfer) appears to be challenged by stricter molecular requirements for mitotic spindle assembly than in other mammals.” Simerly C, et al. Molecular correlates of primate nuclear transfer failures. Science 2003; 300: 297 (behind paywall). Via pdf by K. Illmensee, Journal fur Reproduktionsmedizin und Endocrinologie, an excellent (English) summary of the current state of mammalian cloning.)
Finally, there's the holy grail of adult stem cells: taking an ordinary cell, de-differentiating it back to the point where it can create any cell, and then using it to grow the needed cells or organs -- or a complete new human being. Well, the grail has already been sighted. I started writing this interminable series of posts about stem cells over three months ago, and new research keeps coming out that forces me to rewrite, and add!, whole chunks. Such as the fact that this has been done. They even have a cute mouse they grew from a mouse fibroblast, a type of connective tissue cell. Abstract, Nature, June 6, 2007)
Even more recently as reported in ScienceNews (currently, only the references are freely available), that original lab plus two others have managed consistently to identify completely retagged stem cells. (They use the word "reprogrammed." You might also see it called "reimprinted.") That's a big breakthrough in itself. Selected cells were implanted into an existing early-stage mouse embryo -- which means they're still "cheating" somewhat by using the regulatory processes of natural embryos -- and the fibroblast-derived stem cell formed a baby mouse.
The bad news is that 20% of the fibroblast-derived mice died of cancers. There seems to be a thin line between good stem cells and those that have gone over to the dark side. Who knows, maybe when they solve the problem of stem cells causing cancers they'll solve the problem of all cancers.
Mice, as I've been saying, work rather differently than humans, but, still, it all goes to show that it's just a matter of time before any cell can be turned into an embryo-generating cell. The people I was talking about at the end of Part II really need to get to work on sorting out the difference between potential and actual human beings. They don't have too many years left.
Current applications in medicine
A constant refrain in all these stem cell posts should be "more research needs to be done" because I want to be real clear on the fact that most of this stuff is neither here nor now. However, it's not all somewhere over the mountain. Some of it really is here and now. I'll give some examples, but first a caveat on how likely we are to see these methods widely applied.
Because of the restrictions on embryonic stem cells, all the currently applied therapies use stem cells taken from the person who needs the therapy (called "autologous" cells), so that there are no rejection issues. That also means the therapies have to be individually tailored, which makes them expensive, and makes pharmaceutical companies unhappy. It's the same problem they have with using genomic testing to find the most effective drug for a specific patient. It's also why they try to pretend that any anti-depressant will work in any patient, although that's clearly not the case. The ideal drug for big companies is something expensive that works for everyone. That's how you sell blockbuster profit-makers. So I'm not sure how widespread any of these therapies will become, no matter how successful they are.
Immune system stem cells have been taken from blood, bone marrow, or umbilical cord blood, and grown together with cancer cells from the same patient. That primes the mature immune cells produced in the culture to attack that particular cancer. The mature cells are injected back into the patient, and do a rather amazing job of dissolving tumors. Since it's highly experimental, it's only been used against tumors that would have been fatal otherwise in some brain cancer patients, for instance.
[Stem cells are different from another cutting edge biotech innovation, monoclonal antibodies, but they do share some similar lab techniques, and they tend to show up how little we really know. That last fact was made horribly obvious during safety testing of one monoclonal antibody during which six British volunteers nearly died. Months later, the cause still wasn't known, and that was still true in the last report I saw.]
"Sperm" cells have been made from bone marrow as an infertility treatment. Autologous adult stem cells have been successfully used to block type 1 diabetes (i.e. juvenile diabetes). (Summary of the original research.) Stem cells have been activated in skin to improve wound healing, and activation of specific genes in the cells has also led to the growth of new hair follicles. So the research gets reported as a "cure for baldness." Heart valve repair using stem cells is becoming a reality.
Ethics ... yet one more time
We're at the very beginning of using stem cells in medicine, and we already have treatments for some forms of cancer, blindness, neurodegenerative diseases, diabetes, and the list goes on. In all the talk of stem cells and ethics, I haven't seen much about the ethics of keeping people sick because somebody doesn't think they should have a cure.
The very people going on about ethics are the ones who seem to be ignoring the gigantic ethical issue of forcing people to die for somebody else's beliefs.
Because that's what is going on here. This isn't about the rights of embryos versus adults. This is about one set of adults deciding what it means to be human and then imposing their beliefs on other people. Nobody has proved or can prove that an embryo is a human person. That is a matter of belief. It's something everybody has to decide for themselves. It's something nobody can decide for anyone else.
Imposing beliefs on others is not an individual ethical issue. It's not something we decide for ourselves. It's a huge social ethical issue, and therefore can be and should be prevented by law. When one set of adults starts imposing their beliefs on other people, sometimes fatally so, it runs counter to the bedrock of any free society.
There are laws against that. And if familiarity has bred contempt for the original laws, it's past time to make some new ones.
All three parts posted together at Acid Test
