Still Smarter to Be Lucky

Redwing57 expressed interest in this conversation…I’d like to carry the interesting dialogue forward by tying in halbert and clocknut’s broad side discussion in this thread on stem cell research.   If you are interested in the conversation join in, but as clocknut expressed, let’s please NOT turn it into a conversation on ethics of embryonic stem cells.   In fact, I hope to point out here why the original thread topic is NOT about embryonic stem cells.   I will also bring in dialogue about why stem cell research—adult stem cell research— MAY be the key to solving the elusive “cure” for end-stage castrate-resistant, androgen-independent prostate cancer.     The original post by PDA  in this thread came about because of an article about a statistical model on stem cell division, and that variation in cancer risk among certain tissues can be explained by the number of stem cell divisions, or replications.  (I underline "among certain tissues" because this article did NOT include prostate tissue.)   Cancer is caused by mutations, and mutations can be caused simply by randomness occurring in replication.  (There are other causes of mutations besides random replication...but it can occur just because replication happens so frequently that it's not always perfect; microenvironment conditions may contribute to how frequently the replications cause mutation, but this gets back into environment, etc.)   Stem cells from different types of tissue replicate at different rates.   The more replications that take place, the higher the likelihood of having more mutations, and more mutations translates in this model to more likelihood of cancer based on factors which are completely out of the control of any individual.   [This is where the car-trip analogy comes in…the longer the trip, the more likely you are to have an accident….the more replication, the more likely you are to develop cancer.]     The lifetime risk of getting Islet Pancreatic Cancer is low , but the number of replications that take place in Islet Pancreatic Cancer (IPC) stem cells (as an example taken from the research data) is high , so the RELATIVE risk of IPC (based solely on the “luck” of how rapidly IPC stem cells divide) ends up being high .   (Actually, it is the highest of the 31 tissues studied, as I previously commented in this thread.)   BUT the ABSOLUTE risk of Islet Pancreatic Cancer diagnosis remains low .   This is one of the main points of criticism on the journalism from the article Tall Allen posted; too many have misinterpreted this mathematical model.   The sensationalism of the journalism was criticized, but not the science itself.   Too many of the journalists implied that this study meant something else…which caused many lay-readers to also interpret the results incorrectly.     It appears to have been the case here, and similar to what can be found in discussions, editorials and debates elsewhere, is that the simple mention of “stem cells” can elicit divisive ethical controversies, sometimes leading to the heated political debates which we seek to avoid at this site…and indeed stem cell research HAS critical ethical dimensions.   But to have meaningful conversation here today on the original topic posted by PDA , it is important to differentiate the two main types of stem cells.   Embryonic stem cells are present at the very beginning of embryonic life, and they eventually divide and morph, or differentiate , into cells as different as beating heart muscles, nerve cells that generate and transmit vital signals, pancreas cells that produce insulin, and prostate cells.   Embryonic stem cells give rise to each and every one of the body’s 10 trillion cells.   Adult stem cells are versions of those already-morphed, differentiated cells.   All adult organs appear to possess a small number of stem cells that reside in a special protected region, or niche.   Because most cells in a tissue or organ have a limited life span, stem cells function as a “reserve” of cells that can be moved out of their niche, begin dividing, and ultimately replace dying cells.   This is renewal of tissue cells is healthy growth and keeps us going (and as previously mentioned, some tissues renew cells at a faster/slower rate than others).   The key difference between adult and embryonic stem cells is that embryonic stem cells have the potential to morph into any cell type, the adult stem cell ordinarily only develop into the same cells as their parent organs.   As an illustrative example, adult stem cells from the liver divide to become normal, functioning liver cells, but not brain cells.   Embryonic stem cells could be very valuable in research because of their theoretical ability to differentiate into any cell in the body.   Researchers hope they will one day be able to stimulate embryonic stem cells to differentiate into healthy nerve cells that could be transplanted into patients to replace nerve cells damaged by Parkinson's disease, strokes, or spinal cord injuries.   The controversy surrounds where and how embryonic stem cells are harvested/produced… and we will leave it at that .   The point here is that there really is little or no controversy surrounding adult stem cell research, and clocknut helped make this point in his post, above.     Prostate (adult) stem cells are an immature area of study…this is largely why it was deliberately excluded from the study which PDA originally posted about .   We do know that only a fraction of a percent of cells in the prostate are stem cells, and that they are contained in a niche in the lower, or basal, layer of the prostate’s glandular structures.   It gets a little more theoretical beyond this point…again the understanding is immature.   Current research holds that prostate cancer develops when differentiated, mature prostate cells undergo genetic mutations which permit unrestrained cell multiplication (malignancy) and ultimately allow these cells to spread beyond the prostate.   Normal prostate cells have androgen receptors (ARs) which mediate androgen (male hormone) action in the prostate, BUT the mutated cancer cells have a higher number of androgen receptors (over-expression of ARs).     But (important point!), prostate cancer stem cells have been found to lack ARs.   And PC stem cells are found in higher density in castration-resistant disease.   Androgen ablation therapy may actually promote disease progression by activating normally quiescent cancer stem cells to repopulate the tumor with androgen-independent cells.  These stem cells MAY, indeed, be responsible for androgen-independent advanced PC, and selectively targeting these stem cells could lead to new therapy for those men at the end-stage for whom very little is available today.   With greater understanding of PC stem cells through research, we may reduce or eliminate prostate cancer deaths.   This approach doesn’t stop the development of PC malignancy, but has the potential to be a “cure” for an otherwise chronic condition.     Cool stuff…and again, I’m glad PDA’s posting opened the door to discussion on this topic...even though his original posting had nothing to do with prostate cancer.       Post Edited (JackH) : 1/8/2015 1:28:31 PM (GMT-7)

JackH, I agree that stem cells, and understanding how they work (and fail) are one of the major keys to understanding cancer. I always try to remind myself that we are literally at the zero point of the research process. I suggest that we are years away from really understanding what is happening and how it works. In the mean time, we muddle through with what we know, and what we think we know (which is probably 1% or less of what we, or our children, will know in the future. From what I understand, most of the stem cell research (adult or embryonic) is still trying to figure out the biochemical triggers that direct a stem cell to turn into "whatever" it might become. I remember my daughter telling me that there was a major revelation by a researcher who figured out that one particular process required the stem cell to be in the dark and at a very specific temperature. Easy inside the body, harder in a lab.

That being said, reading about research in the popular press is risky, largely because their goal is to sell papers and magazines, not to actually pass on good rational information.

Witness, the difference between using "luck" and "random event" in a headline.

I have to admit that I like the notion of "bad luck" to explain at least some and possibly a narrow majority of cancers, including prostate cancer. Yes, it is related fairly strongly to the metabolic syndrome (obesity, poorly controlled blood sugar and triglycerides, and high blood pressure) but we all know someone thin and athletic who was diagnosed, and we know lots and lots of sedentary, waddling lard-asses who never were.

I seem to disappoint JackH and a few others by being such a poor huckster for prevention but I respond poorly to hucksterism myself and I am trying to encourage other people like me. The fact of the matter is that at least some prostate cancer is caused by factors we don't understand and can't control. It may not be three quarters but I don't care about the numbers. What I care about is for men with prostate cancer to understand that it is not their fault that they have it and, what's more, they must understand, too, that a healthy lifestyle improves their odds, even after diagnosis, and the fact that they have been unlucky once doesn't mean that a healthy lifestyle won't help them now.

And, to Jerry's point, if you start from quantum-level physics it is all randomness (which we might as well call luck) and determinism is an illusion caused by our knowing the odds. An elementary particle can do pretty much what it wants. Atoms are a bit easier to predict but radioactive decay can't be predicted at the level of individual atoms. By the time you get to macro phenomena the number of particles participating is so high that most of our statistical approximations can be mistaken for physical laws.

DNA molecules are big enough that it is tempting to think of their behavior as deterministic but small enough to possibly be wrong about that.