Cysteine-cysteine chemokine receptor 5 (CCR5) is found in the cell membranes of many types of mammalian cells, including nerve cells and white blood cells.1,2 The role of CCR5 is to allow entry of chemokines into the cell3—chemokines are involved in signaling the body’s inflammation response to injuries.4
The gene that codes for CCR5 is situated on human chromosome 3. Various mutations of the CCR5 gene are known that result in damage to the expressed receptor. One of the mutant forms of the gene is CCR5-delta32, which results from deletion of a particular sequence of 32 base-pairs. This mutant form of the gene results in a receptor so damaged that it no longer functions. But surprisingly, this does not appear to be harmful:
Yersinia pestis seen at 2000x magnification. This bacterium, carried and spread by fleas, is generally thought to have been the cause of millions of deaths.
Moreover, this mutation can be advantageous to those individuals who carry it. The virus HIV normally enters a cell via its CCR5 receptors, especially in the initial stage of a person becoming infected.5 But in people with receptors crippled by the CCR5-delta32 mutation, entry of HIV by this means is blocked, providing immunity to AIDS for homozygous carriers and greatly slowing progress of the disease in heterozygous carriers.6–8
Up to 20%8 of ethnic western Europeans carry this mutation, which is rare or absent in other ethnic groups.9–11 This suggests that the CCR5-delta32 mutation was strongly selected for sometime during European history. Some researchers have proposed that the plague epidemics that repeatedly swept Europe during the Middle Ages were responsible.12 However, recent experiments in mice suggest that Yersinia pestis, the cause of plague, can infect mammalian cells by other means13–15 and so some scientists have proposed that smallpox, which is caused by the variola virus, was the selection agent that historically caused CCR5-delta32 carriers to proliferate in Europe.15
With the advantage of providing full or partial immunity to certain diseases, and with no apparent disadvantages [But see Addendum March 2009. Ed.], CCR5-delta32 can be considered a prime example of a beneficial mutation—a mutation that decreases the information content of the genome and degrades the functionality of the organism, yet provides a tangible benefit.19
To date over 10,000 specific disease-causing mutations of the human genome have been identified.20 In contrast, only a handful of beneficial mutations have been discovered, none of which involve an increase in genetic information as required by evolution. All this is highly consistent with the biblical account of a very good creation21 followed by the Fall,22 and a subsequent six millennia23 of cumulative physical degeneration.24 However, it clashes irreconcilably with the evolutionary view that the accumulation of mutations over time brings about upward evolution (increasing functional complexity).
In God’s original creation, before the Fall and the Curse, the CCR5 receptor would not have constituted an entryway for pathogens. It may be that infectious agents like HIV only became pathogenic after degeneration from their original ‘very good’ created state. Or it may be that humans did not live in the same environment as such pathogens and so were just not exposed to them. Perhaps both these scenarios apply (see The origin of bubonic plague on p. 7). We look forward to God’s promised Restoration, when there will be no more mutation, disease or suffering.25
To infect immune cells, HIV must first bind to chemokine receptors. Researchers discovered in 1996 that people who had a naturally occurring mutation in their genes for one of these, CCR5, were strongly protected from developing AIDS—or even becoming infected in the first place—and suffered no ill effects from lacking the receptor.
Sangamo specializes in developing enzymes called zinc finger nucleases that can bind to genes, clip their DNA, and repair mutations (Science, 23 December 2005, p. 1894). But for the HIV gene therapy, they’ve created a nuclease to specifically disrupt the CCR5 gene in the same manner as the natural mutation. In the new trial, researchers will put the gene for this zinc finger nuclease into an adenovirus vector, transduce harvested CD4+ T cells of HIV-infected people, and infuse those cells back. June says this is the first gene-therapy experiment that aims to create a phenotype that’s known to confer disease resistance.’26
A reader alerted us to the fact that at least one drawback associated with this mutation has been found. The CCR5-delta32 mutation is strongly associated with a chronic and potentially life-threatening liver disease: