Multi-cellular organisms are composed of cells belonging to a wide variety of types. Careful studies of the behavior and dynamics of some of these cellular populations have revealed that we ourselves are being shaped and influenced by adaptive evolutionary principles during the course of our individual lives. Here we discuss two examples to illustrate the application of basic evolutionary principles to these medically significant phenomena.
(a) Humoral Immunity
The immune response concerns the reaction of the body (self) to invasion by foreign substances (non-self). In the context of humoral immunity, foreign substances (perhaps viruses or bacteria or parts thereof) known as antigens stimulate B-lymphocyte cells to produce molecules known as antibodies. Antibodies react with antigens to tag them for further immunological responses. The details of the antibody-antigen reaction are instructive for present purposes.
A specific antibody, carried by a B-lymphocyte, is capable of "recognizing" (by chemical binding) a limited range of antigenic molecular shapes. For a given antigen, some antibodies never bind, some do rarely, and some will bind to the antigen virtually every time they encounter it. There is enormous variation and diversity in the antibody population – the system is capable of recognizing more than 108 antigen shapes. Once an antibody binds to an antigen, the B-cell can receive a second signal from a T cell. This combination of signals stimulates the particular B-lymphocyte to divide (mitosis) and make daughters of itself. The proportion of these particular B-cells thus increase in the lymphocyte population, which then, in turn, create more of the appropriate antibody. The B-lymphocyte population displays variation and, depending on selective antigenic binding and signals from other lymphocytes, differential reproductive success relative to those B-lymphocytes that failed to bind to the current invader.
Some B-lymphocytes become factories for the production of large numbers of antibodies to fight the current infection. But other successful B-lymphocytes remain in circulation in the body, providing the immune system with a memory of that particular antigen shape. This phenomenon explains why the immune response on subsequent re-infection is faster than the initial response. These binding characteristics of the descendents of the original successful B-lymphocytes are thus genuine Darwinian adaptations, in this case for immunological function. Indeed, Parham has observed:
At some point this century the experimental biologists, in an echo of Henry Ford, divorced themselves intellectually from the evolutionary biologists. This artificial and regrettable separation remains with us today. For the immunologists it was always a sham, for the very foundations of their subject are built upon stimulation, selection and adaptive change. Now we see clearly the immune system for what it is, a vast laboratory of high speed evolution. By recombination, mutation, insertion and deletion, gene fragments are packaged by lymphocytes, forming populations of receptors that compete to grab hold of antigen. Those that succeed get to reproduce their progeny, if antibodies, submit to further rounds of mutation and selection. There is no going back and the destiny of each and every immune system is to become unique, the product of its encounters with antigen and the order in which they happen. This all happens in somatic tissues, in a time frame of weeks and is perhaps too vulgar, too fast, for traditional tastes to be even called evolution [[13]:373].
Having a fast, adaptive immune system is clearly advantageous in a world where we are confronted with rapidly evolving pathogens and parasites. But, as we observed earlier, evolution occurs with no eye to the future. This can be illustrated through a consideration of the pathological phenomenon of cancer.
(b) Cancer
In multi-cellular organisms, such as ourselves, there is a sort of "social contract" between cells of various specialized types (liver cells, kidney cells, etc). These cells are, for the most part, genetically identical. Kidney cells differ from liver cells primarily with respect to differential patterns of gene activation, not the genes themselves. Somatic cells of various specialized types cooperate (and ultimately perish with the death of the organism) so that the specialized reproductive cells (gametes) can get genes identical by descent into the next generation. Cancer cells can be thought of as outlaws that violate the multi-cellular social contract. They replicate at the expense of their neighbors and ultimately at the expense of the organism bearing them.
The formation of a cancer cell is typically a multi-step process in which several mutant alleles must be acquired. The probability of a given cell becoming a cancer cell is small, but there are billions of cells – by analogy, the probability that you win the State lottery is small, but when millions of tickets have been sold, it is likely that somebody will win. Cancer cells begin as mutant versions of healthy cells, and they are cells that have acquired the ability to activate their own reproduction, producing almost identical clones. The reproductive process is not perfect, and the progeny of the initial cancer cell typically constitute a population of cells displaying variation with respect to heritable characteristics. The descendents of these cells themselves acquire mutations and eventually some may acquire the ability to migrate to new locations, thereby departing from the confines of their cellular origins. The end result is metastatic cancer. Untreated, and barring spontaneous remission, unrestrained cellular proliferation, with or without metastasis, typically brings about the failure of critical organ systems and death.
In the treatment of cancer using chemotherapy, an all too familiar evolutionary saga plays itself out. Chemotherapeutic agents are differential poisons that target speedily replicating cancer cells. Unfortunately, they also can affect other speedily replicating healthy cells (such as epithelial cells), which is why chemotherapy can have such awful side-effects. If you are lucky, the chemical agent eliminates all the cancer cells. Alas, quite often treatment reduces the cancer cell population to a few hardy survivors while giving the appearance of remission. But this small, now selectively hardy population may gradually repopulate the patient. The resultant growing population bears the genetic inheritance that enabled the cancer cells to survive the initial therapeutic assault – a genetic inheritance resulting in the evolution of drug resistance. Now the oncologist is required to try new agents, until they, too, are rendered ineffective through the adaptive evolution of populations of the cancer cells in question. As Greaves has observed:
. . . cancer. . . is a form of evolution played by the same Darwinian ground rules as apply to evolution in general and particularly for asexually propagating species. The essential game plan is progressive diversification by mutation within a clone, coupled with selection of individual cells on the basis of reproductive and survival fitness, endorsed by their particular gene set. Its evolution on the fast track [[15]:39].
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