Cystic Fibrosis as a Kludgy Adaptation

The dear departed Richard Allan Glenn, also known as WinAce, suffered from Cystic Fibrosis. And in honor of him, I have written this essay, I will discuss how that disease works and what brought it into existence.

Cystic fibrosis has several symptoms, but the most important ones are secretion of excessively thick mucus in the lungs and elsewhere. CF patients also have difficulty digesting food and absorbing nutrients, and they often have stunted growth.

Thick mucus in the lungs not only interferes with breathing, it can become infected, and Allan had suffered from a particularly difficult lung infection, by the bacterium Burkholderia cepacia. In the last months of his life, sympathetic friends had organized a fundraiser to finance a lung transplant for him, so he could have unclogged lungs, but he died before that fundraiser got very far.

Cystic fibrosis is inherited, and it is caused by versions of a gene that makes defective versions of a protein called the Cystic Fibrosis Transmembrane Conductance Regulator, or CFTR for short. This protein pumps chloride ions out of a cell, where their negative charge induces sodium ions to follow them. The greater ion concentration then induces water to follow, thus making CFTR a water pump. This protein is produced by cells in various epithelial (surface) membranes, like the skin, lungs, digestive tract, and reproductive tract.

When CFTR is defective, it pumps chlorine less efficiently, thus pumping water less efficiently and making mucus much thicker. It also makes sweat thicker and saltier, thus making possible a common test for CF: the sweat test.

The CF-causing mutations of CFTR are remarkably common in some populations, ranging from 1/90 in Asian populations to 1/25 in European populations, which has led to the heterozygote-advantage hypothesis, an advantage in having copies of a gene that differ (different alleles). In this hypothesis, a normal version N and a defective version D together offer some protection against a disease organism or other adverse condition. However, a ND – ND cross produces on average 1/4 NN’s, 1/2 ND’s, and 1/4 DD’s, thus producing a continual supply of individuals suffering the effects of D.

Cystic fibrosis is one of several genetic defects that are likely maintained by the heterozygote-advantage mechanism.

Sickle-cell anemia is a classic example; it is a result of being homozygous (having all gene copies the same) in a version of a gene for a hemoglobin part. The resulting defective protein makes red blood cells get abnormal shapes, thus the name of the disease. However, that protein is not very palatable to malaria protozoans, and the ND case of having normal hemoglobin present makes the red blood cells normal, while deterring the malaria bugs.

Thalassemia likely provides protection against malaria in a similar fashion, though this disease involves too little hemoglobin production, rather than production of abnormal hemoglobin.

Tay-Sachs disease is caused by deficiencies in the enzyme hexosaminidase A, which breaks down fatty-acid derivatives called gangliosides. This makes gangliosides accumulate in nerve cells, causing the disease’s neurological symptoms. There has been some suggestion that being heterozygous in Tay-Sachs defects can protect against tuberculosis.

Hemochromatosis is excessive iron absorption and storage. Men get it more often than women, because they don’t lose iron as a result of menstruating. It is likely an adaptation to an iron-deficient diet, and men getting hemochromatosis is a less serious loss than women getting iron deficiency, since men are less of a reproductive bottleneck than women.

Some other diseases, like phenylketonuria and glucose-6-phosphate dehydrogenase deficiency, may possibly have this origin.

There are similar adaptations that are responsible for some diseases that are not maintained by heterozygote advantage.

Diabetes mellitus, diabetes for short, is excessive retention of glucose in the blood. According to the “thrifty gene hypothesis”, it has evolved as a mechanism to survive famines, by making glucose retention super efficient. But when one is well-fed, that super efficiency causes diabetes.

For many allergies, a plausible hypothesis is the “hygiene hypothesis”, in which excessive cleanliness deprives the immune system of its usual targets, microbes and small parasitic worms. It then starts tilting at such windmills as pollen, pet dander, various foods, etc.

Turning to cystic fibrosis itself, it is likely a protection against diarrhea, which is caused by excessive pumping out of water. Defective water pumping would thus protect against excessive water pumping.

More broadly, sickle-cell anemia, diabetes, cystic fibrosis, etc. are rather kludgy adaptations, and not the sort of perfect designs that one would expect from some supposed super designer. Instead, they look like what a designer with rather limited powers might design. A super designer would likely be smart enough to avoid solutions with the troublesome side effects that I had described.

Turning to what the CF gene variants likely protect against, diarrhea, we find that it is often caused by various microbes, like the cholera bug Vibrio cholerae. Such diarrhea can cause enough water loss to be fatal to its sufferer, so protecting against it can be a convenient adaptation.

Causing diarrhea may seem like sadism on the part of such a microbe, but it helps to spread that microbe. Likewise, common-cold viruses spread themselves by making their hosts cough. And for extreme sadism, it is hard to compete with the rabies virus. It makes its hosts very irritable and willing to bite, and it spreads to another host in a resulting bite.

Some such manipulations can get very fancy.

The lancet liver fluke, the trematode Dicrocoelium dendriticum, has a remarkable one. When this bug infects an ant, it tweaks the ant’s brain and makes that ant climb up a grass leaf. That ant may then be eaten by a grazer like a cow or a sheep, which the fluke can then infect.

Toxoplasmosis is caused by the parasitic protozoan Toxoplasma gondii, which makes small-rodent hosts less fearful and more curious. This makes them easier for cats to catch and eat, enabling the Toxoplasma bugs to spread to those cats.


These host manipulations are what Richard Dawkins has called the “extended phenotype”; an organism’s genes can have effects that extend beyond the organism itself and into its environment. Richard Dawkins has gone on record as considering the extended-phenotype concept his greatest contribution to evolutionary biology.

WinAce himself had mentioned rabies in his big compendium of organisms with nasty features in Organisms that Look Designed. These organisms’ notable features are far from what an omnibenevolent designer would design. Instead, such features are convenient for the organisms that induce them, even if not for the organisms that they affect, including organisms that host them.


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