Yesterday, reader StephenB suggested that I write about what I thought might be the next big medical cure coming our way—he suggested cancer, Alzheimer’s, and Parkinson’s diseases as possible contenders—and what I thought the “shape” of such a cure might be. I thought this was an interesting point of departure for a discussion blog, and I appreciate the response to my request for topics.
[I’ll give a quick “disclaimer” at the beginning: I’ve had another poor night. Either from the stress of Monday night or something I ate yesterday (or both, or something else entirely) I was up a lot of last night with reflux, nausea, and vomiting. So I hope I’m reasonably coherent as I write, and I apologize if my skills suffer.]
One hears often of the notion of a “cure for cancer”, for understandable reasons; cancer is a terrifying and horrible thing, and most people would like to see it gone. However, my prediction is that there will never be “a” cure for cancer, except perhaps if we develop nanotechnology of sufficient complexity and reliability that we are able to program nanomachines unerringly to tell the difference between malignant and non-malignant cells, then destroy the malignant ones and remove their remains neatly from the body without causing local complications. That’s a tall order, but it’s really the only “one” way to target and cure, in principle, all cancers.
Though “cancer” is one word, and there are commonalities in the diseases that word represents, most people know that there are many types of cancers—e.g., skin, colon, lung, breast, brain, liver, pancreatic, and so on—and at least some people know that, even within the broader categories there are numerous subtypes. But every case of cancer is literally a different disease in a very real sense, and indeed, within one person, a single cancer can become, effectively, more than one disease.
We each* start out as a single fertilized egg cell, but by adulthood, our bodies have tens of trillions of cells, a clear demonstration of the power of exponential expansion. Even as adults, of course, we do not have a static population of cells; there is ongoing growth, cell division/reproduction, and of course, cell death. This varies from tissue to tissue, from moment to moment, from cell type to cell type, under the influence of various local and distant messengers, ultimately controlled by the body’s DNA.
Whenever a cell replicates, it makes a copy of its DNA, and one of each copy is sent into each daughter cell. There are billions of base pairs in the human genome, so there are lots of opportunities for copying errors. Thankfully, the cell’s proofreading “technology” is amazingly good, and errors are few and far between. But they are not nonexistent. Cosmic rays, toxins, other forms of radiation, prolonged inflammation, and simple chance, can all lead to errors in the replication of a precursor cell’s DNA, giving rise to a daughter cell with mutations, and when there are trillions of cells dividing, there are bound to be a number of them.
The consequences of such errors are highly variable. Many of them do absolutely nothing, since they happen in portions of the genome that are not active in that daughter cell’s tissue type, or are in areas of “junk” DNA in the cell, or in some other way are inconsequential to the subsequent population of cells. Others, if in just the wrong location, can be rapidly lethal to a daughter cell. Most, though, are somewhere in between these two extremes.
The rate of cell division/reproduction in the body is intricately controlled, by the proteins and receptors in that cell, and the genes that code for them, and that code for factors that influence other portions of the genome of a given cell, and that make it sensitive or insensitive to hormonal or other factors that promote or inhibit cell division. If a mutation in one of the regions of the cell that is involved in this regulatory process—either increasing the tendency to grow and divide or diminishing the sensitivity to signals that inhibit division—a cell can become prone to grow and divide more rapidly than would be ideal or normal for that tissue. Any given error is likely to have a relatively minor effect, but it doesn’t take much of an effect to lead to a significant increase in the number of cells in a given cell type eventually—again, this is the power of exponential processes.
A cell line that is reproducing more rapidly will have more opportunities for errors in the DNA reproduction of its many daughter cells. These new errors are no more likely to be positive, negative, or neutral generally than any other replication errors anywhere else in the body, but increased rate of growth means more opportunities** for mistakes.
If a second mistake in one of the potentially millions (or more) of daughter cells of the initial cell makes it yet more prone to divide rapidly than even the first population of mutated cells, then that population will grow and outpace the parent cells. There can be more than one such daughter populations of cells. And as the rate of replication/growth/division increases in a given population of cells, we have an increased chance of more errors occurring. Those that become too deleterious will be weeded out. Those that are neutral will not change anything in the short term (though some can make subsequent mutations more prone to cause increased growth rates). But the ones that increase the rate of growth and division will rapidly come to dominate.
This is very much a microcosm of evolution by natural selection, and is a demonstration of the fact that such evolution is blind to the future. In a sense, the mutated, rapidly dividing cells are more successful than their more well-behaved, non-mutated—non-malignant—sister cells. They outcompete for resources*** against “healthy” cells in many cases, and when they gather into large enough masses, they can cause direct physical impairments to the normal function of an organism. They can also produce hormones and proteins themselves, and can thus cause dysregulation of the body in which they reside in many ways.
Because they tend to accumulate more and more errors, they tend to become more dysfunctional over time. And, of course, any new mutations in a subset of tumor cells that makes it more prone to divide unchecked, or that makes it more prone to break loose from its place of origin and spread through the blood and/or lymph of the body will rapidly become overrepresented.
This is the general story of the occurrence of a cancer. The body is not without its defenses against malignant cells—the immune system will attack and destroy mutated cells if it recognizes them as such—but they are not perfect, nor would it behoove evolution (on the large scale) to select for such a strictly effective immune system, since all resources are always finite, and overactive immunity can cause disease in its own right.
But the specific nature of any given cancer is unique in many ways. First of all, cancers arise in the body and genes of a human being, each of which is thoroughly unique in its specific genotype from every other human who has ever lived (other than identical twins). Then, of course, more changes develop as more mutations occur in daughter cells. Each tumor, each cancer, is truly a singular, unique disease in all the history of life. Of course, tumors from specific tissues will have characteristics born of those tissues, at least at the start. Leukemias tend to present quite differently from a glioblastoma or a hepatoma.
Because of these differences, the best treatments for specific cancers, even of classes of cancers, is different. The fundamental difficulty in treating cancer is that you are trying to stop the growth and division—to kill—cells that are more or less just altered human cells, not all that different from their source cells. So any chemical or other intervention that is toxic to a cancer cell is likely to be toxic to many other cells in the body. This is why chemotherapy, and radiation therapy, and other therapies are often so debilitating, and can be life-threatening in their own right. Of course, if one finds a tumor early enough, when it is quite localized, before any cells have broken loose—“metastasized”—to the rest of the body, then surgical removal can be literally curative.
Other than in such circumstances, the treatment of cancer is perilous, though not treating it is usually more so. Everything from toxic chemicals to immune boosters, to blockers of hormones to which some cancers are responsive, to local radiation are used, but it is difficult to target mutated cells without harming the native cells to at least some degree.
In certain cases of leukemia, one can literally give a lethal dose of chemo and/or radiation that kills the bone marrow of a person whose system has been overwhelmed by malignant white blood cells, then giving a “bone marrow transplant”, which nowadays can sometimes come from purified bone marrow from the patient—thus avoiding graft-versus-host diseases—and there can be cures. But it is obviously still a traumatic process, and is not without risk, even with auto-grafts.
So, as I said at the beginning, there is not likely to be any one “cure” for cancer, ever, or at least until we have developed technology that can, more or less inerrantly, recognize and directly remove malignant cells. This is probably still quite a long way off, though progress can occasionally be surprising.
One useful thing cancer does is give us an object lesson, on a single-body scale, that it is entirely possible for cell lines—and for organisms—to evolve, via apparent extreme success, completely into extinction. It’s worth pondering, because it happens often, in untreated cancers, and it has happened on the scale of species at various times in natural history. Evolution doesn’t think ahead, either at the cellular level, the organismal level, or the species/ecosystem level. Humans, on the other hand, can think ahead, and would be well served to take a cue from the tragedy of cancer that human continuation is not guaranteed merely because the species has been so successful so far.
Anyway, that’s a long enough post for today. I won’t address matters of Parkinson’s Disease or Alzheimer’s now, though they are interesting, and quite different sorts of diseases than cancers are. I may discuss them tomorrow, though I might skip to Friday. But I am again thankful to StephenB for the suggestion/request, and I encourage others to share their recommendations and curiosities. Topics don’t have to be about medicine or biology, though those are my areas of greatest professional expertise. I’m pretty well versed in many areas of physics, and some areas of mathematics, and I enjoy some philosophy and psychology, and—of course—the reading and writing of fiction.
Thanks again.
*I’m excluding the vanishingly rare, and possibly apocryphal, cases of fused fraternal twins.
**There are also people who have, at baseline, certain genes that make them more prone to such rapid replication, or to errors in DNA replication, or to increased sensitivity to growth factors of various kinds, and so on. These are people who have higher risks of various kinds of cancer, but even in them, it is not an absolute matter.
***Most tissues in the body have the inherent capacity and tendency to stimulate the development of blood vessels to provide their nutrients and take away their wastes. Cancer cells are no exception, or rather, the ones that are do not tend to survive. Again, it is a case of natural selection for those cell lines that are most prone to multiply and grow and gain local resources.
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Robert Elessar 