Survival of the fittest? Not so fast

The phrase "survival of the fittest" was coined by Herbert Spencer, a British social philosopher, to accentuate the differences in survivability of the different social classes. Inevitably, the notion fed into the belief of the existence of more advanced individuals and cultures, and served to justify colonization (of "inferior" societies) and imperialism.

To Spencer, the concept was equivalent to what Charles Darwin was then calling "natural selection, or the preservation of favored races in the struggle for life." The phrase was later adopted and widely used by Charles Darwin himself. The phrase can be applied, not only to individuals and groups, but to cells and molecules as well.

Survival and perpetuation of one’s genes are every organism’s most immediate goals. There is an unending struggle for survival among the many organisms in our world and the most able to compete – the "fittest" – have the highest chances of winning. The many different organisms that can be found in our world today are the result of eons of change, competition, and selection of the "fittest" (in other words, evolution), and the present-day organisms represent the forms that are best adapted to the prevailing conditions.

Who are the "fittest"? Are they the strongest? The healthiest? The most intelligent? All of the preceding? None of the preceding? In fact, the "prevailing conditions" are what define who are the "fittest" (and who will survive).

In a situation where there is shortage of food, those who do not require much food – the smaller individuals – will more likely survive. In situations where there is competition for territory, the better fighters – the bigger and stronger, or those who have better weapons – will more likely win.

If two individuals – one fat, one lean – are dumped in the ocean, one will probably float while hardly moving a muscle, whereas the other may sink straight to the bottom. If instead they are dumped in lion country, the cats will more likely end up feasting on meat generously marbled with fat, instead of lean meat. (I’m obviously trying to be funny here.)

But really it all depends on the "prevailing conditions."

That is true also in the cellular and molecular world of biology. The "fittest" among the molecules and cells, the ones chosen by Nature to prevail and to persist, are defined by the circumstances. Let me illustrate.

Recognition is the hallmark of biology. Biological molecules and cells do not associate randomly – otherwise, our world will be chaotic. Rather, molecules (and cells) interact specifically with the entities (other molecules and cells) they are meant to interact with. There is a pattern to which we conform. There is order and structure. In situations where molecules are meant to bind one another, the molecules which best fit each other and whose interaction serves the intended purpose would be expected to be favored and kept during the course of evolution.

A part of us in which recognition is very important is our immune system. The system has to be able to distinguish between beneficial and harmful (food is good, germs are bad) – we tolerate the first, we rid ourselves of the second. The system also has to be able to distinguish between our own cells (and molecules) and foreign cells (and substances) – we leave our own cells alone, we kill the invaders. How does the immune system accomplish this?

Three types of molecules are primarily responsible for immune recognition: the antibodies, the T cell receptors (TCRs) for antigen, and the Major Histocompatibility Complex (MHC) molecules. A membrane form of antibodies is initially found on the surface of B lymphocytes (cells that complete their differentiation in the bone marrow) and then a soluble form of antibodies is secreted after the B cells have gone through several cycles of development (maturation). The TCRs are found on the surface of T lymphocytes (cells that complete their differentiation in the thymus and of which two types will be mentioned here: the helper T cell and the killer T cell). MHC molecules are present on the surface of all cells, except those which no longer synthesize protein (for example, red blood cells). Two types of MHC molecules are of interest here: MHC Class I, which is recognized by killer T cells, and MHC Class II, which is recognized by helper T cells.

When they are first formed (in B cells and found in membrane form on the surface of the cells), antibodies have low affinity (strength of binding) and are not specific for anything (binding is said to be specific if it is to only one ligand). When a foreign substance (antigen) gets inside us, there may be B cells that by chance are able to bind to it, even though only weakly. Those B cells will internalize the antigen, break it up into pieces (peptides) and then display the peptides on their surface, bound to MHC Class II molecules. Helper T cells will then come along and if there is a helper T cell whose TCR can bind to the MHC:peptide complex, the T cell will then secrete molecules directed at the B cell, causing the latter to divide. When a B cell divides, its antibody genes undergo hypermutation (mutation at a very rapid rate). Once again, by chance, antibodies on the daughter B cells may bind the antigen – more strongly this time. Those daughter B cells are then "selected," because of their higher affinity, to be activated by helper T cells. The cycle is repeated until, in the end, we have B cells producing antibodies that are specific for the antigen and are able to bind to it with high affinity. The "best" antibodies then are characterized by high affinity for antigen. (B cells that bind to our own molecules are "killed" before they leave the bone marrow.)

For TCRs, the criterion for which are the "best" is quite different. TCRs bind to both the MHC molecule AND the bound peptide. If the binding of the TCR to the MHC molecule is too strong, a helper T cell could activate a B cell that is not displaying the right peptide, or kill the cell, if the T cell is of the killer type and the MHC molecule is of Class I; either of these events would be disastrous. The "best" TCRs then are characteraized by only medium-strength affinity. (As in the case of B cells, T cells that bind to our own peptides are "killed" before they leave the thymus.)

Many other examples abound that demonstrate that there is no easy answer to the question of what constitutes "fitness." So if someone asks which individuals, cultures, organisms or molecules are the "fittest" and best suited for survival, a good response would be: "It depends."

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Eduardo A. Padlan has a Ph.D. in Biophysics and was a research scientist at the (US) National Institutes of Health until his retirement in 2000. He is currently an Adjunct Professor in the Marine Science Institute, College of Science, University of the Philippines Diliman. He is a Corresponding Member of the National Academy of Science and Technology, Philippines. He can be reached at [email protected] or at [email protected].