Malaria, caused by a mosquito-borne parasite, Plasmodium falciparum, is one of humanity's most serious diseases, causing 500 million infections annually worldwide, and about one million deaths. . A recent study once again underlined the steep cost of "natural" protection.

Michael Behe's recent book, Edge of Evolution, addressed the long, vicious warfare between the human red blood cell and the parasite. In ten thousand years of generations, neither side has used natural selection acting on random mutations (Darwin's mechanism) to evolve very satisfactory solutions for overcoming the defenses of the other side.

For example, carriers of sickle cell anemia have some protection, but only at the cost of transmitting two copies of the deadly mutation to children. Hence Behe describes the conflict as trench warfare, in which each side harms the other without really prevailing.

And that's pretty much what a recent study has also found. University of Toronto researcher Kevin Kain's team reported that people who were either short of the enzyme known as pyruvate kinase or else carry the genetic mutation that causes the shortage are better able to fight malaria. Their red blood cells resisted the parasite's invasion better. Also, those cells that did not resist effectively were more likely to be destroyed by macrophages than the cells of infected control subjects. (Macrophages are white blood cells that maintain body health by eating suspicious cells and foreign organisms.)

However, the pyruvate kinase enzyme is needed to produce energy, so lacking it - or passing on a tendency to lack it - is not a very satisfactory solution. As Behe notes, it is "another example of a beneficial mutation turning out to be a degradative mutation."

Dr. Kain hopes, however, that this kind of information will help us design better protection against malaria, as he told ScienceDaily:

"Understanding how these mutations make us more resistant to malaria can help us design innovative new strategies to prevent or treat severe malaria in places such as sub-Saharan Africa," says researcher Kevin Kain, a Professor out of the Department of Medicine at U of T and one of the lead researchers on the project. "Our research shows that people who have an enzyme deficiency or those who carry the gene trait for this deficiency may be protected from severe and fatal malaria."

What we are mainly learning from the study of malaria is that waiting for evolution by natural selection to help us is not satisfactory because accidental mutations are usually bad in themselves.

As Dr. Kain told Insider Medicine's Dr. Susan Sharma, those patients who had both copies of the mutation that knocks out pyruvate kinase "are probably too ill to benefit from this mutation", though relatives who are carriers do get some benefit. The study was published in the New England Journal of Medicine (April 24).

The study and resources

Pyruvate Kinase Deficiency and Malaria Kodjo Ayi, Gundula Min-Oo, Lena Serghides, Maryanne Crockett, Melanie Kirby-Allen, Ian Quirt, Philippe Gros, and Kevin C. Kain. The New England Journal of Medicine, 358(17), April 24 2008, 1805-1810. SUMMARY: Malaria that is caused by Plasmodium falciparum is a significant global health problem. Genetic characteristics of the host influence the severity of disease and the ultimate outcome of infection, and there is evidence of coevolution of the plasmodium parasite with its host. In humans, pyruvate kinase deficiency is the second most common erythrocyte enzyme disorder. Here, we show that pyruvate kinase deficiency provides protection against infection and replication of P. falciparum in human erythrocytes, raising the possibility that mutant pyruvate kinase alleles may confer a protective advantage against malaria in human populations in areas where the disease is endemic. 

Resources:

How malaria infects

"More trench warfare in the fight against malaria" by David Tyler

A medical explanation of the study findings from InsiderMedicine.com

Note: Malaria is rare in colder regions because where temperatures are regularly below 20 degrees Celsius, the malaria parasite cannot function properly. Behe observes in Edge of Evolution that in its known history, the malaria parasite has never evolved a means of overcoming this limitation.