On the utility of evolution in experimental biology and medicine

A recurring theme amongst ID antievolutionists holds that evolution really doesn’t contribute useful directions or concepts in the realm of biology or medicine. Philip Skell regurgitates the theme in a recent commentary in Forbes magazine:

“Examining the major advances in biological knowledge, one fails to find any real connection between biological history and the experimental designs that have produced today’s cornucopia of knowledge of how the great variety of living organisms perform their functions. It is our knowledge of how these organisms actually operate, not speculations about how they may have arisen millions of years ago, that is essential to doctors, veterinarians, farmers and other practitioners of biological science.”

And later:

“The essence of the theory of evolution is the hypothesis that historical diversity is the consequence of natural selection acting on variations. Regardless of the verity it holds for explaining biohistory, it offers no help to the experimenter–who is concerned, for example, with the goal of finding or synthesizing a new antibiotic, or how it can disable a disease-producing organism, what dosages are required and which individuals will not tolerate it. Studying biohistory is, at best, an entertaining distraction from the goals of a working biologist.”

The blogosphere (and probably print media) are replete with summaries and specific cases that show Skell’s assertions to be a crock. This essay summarizes one such example. I have chosen this one because it refutes, specifically, the claim that an understanding of the evolutionary history of an organism “offers no help to the experimenter–who is concerned, for example, with the goal of finding or synthesizing a new antibiotic, or how it can disable a disease-producing organism”. It also ties Skell’s uninformed comments in with another subject that causes ID antievolutionists much consternation - the origins and evolution of organelles.

In the 1990’s, two parallel, seemingly unrelated areas of research came together in a most remarkable way; moreover, they were tied together by explicit evolutionary connections and reasoning. One field concerned the nature of the Apicomplexa, a group of protists that includes some of the most serious and problematic of parasites of humans. For example, the malaria parasite Plasmodium falciparum is a member of this group of organisms. The Apicomplexa possess (and require for survival) a novel organelle, the apicoplast. In the ‘90’s, it was discovered that the apicoplast is related to another organelle, the chloroplast. As Kohler et al. stated in 1997:

“A plastid of probable green algal origin in Apicomplexan parasites.

Kohler S, Delwiche CF, Denny PW, Tilney LG, Webster P, Wilson RJ, Palmer JD, Roos DS.

Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.

Protozoan parasites of the phylum Apicomplexa contain three genetic elements: the nuclear and mitochondrial genomes characteristic of virtually all eukaryotic cells and a 35-kilobase circular extrachromosomal DNA. In situ hybridization techniques were used to localize the 35-kilobase DNA of Toxoplasma gondii to a discrete organelle surrounded by four membranes. Phylogenetic analysis of the tufA gene encoded by the 35-kilobase genomes of coccidians T. gondii and Eimeria tenella and the malaria parasite Plasmodium falciparum grouped this organellar genome with cyanobacteria and plastids, showing consistent clustering with green algal plastids. Taken together, these observations indicate that the Apicomplexa acquired a plastid by secondary endosymbiosis, probably from a green alga.”

In the meantime, scientists working in a different field were discovering interesting things about chloroplasts, and especially about the unique metabolic capabilities these organelles bring to the plant cell. Specifically, it was discovered that plastids possess a prokaryotic pathway for the biosynthesis of isoprenoids, the precursors of sterols and myriads of secondary metabolites in plants. This is in addition to the more usual pathway known in humans, a pathway also found in plants. These pathways are, respectively, the non-mevalonate and mevalonate pathways.

The apicoplast, which is needed by the parasite, became an obvious new target for therapies. This is where the two lines of research summarized in preceding paragraphs came together, linked through decidedly evolutionary reasoning. Briefly, several groups followed an obvious line of thought - since the parasite has an organelle that is evolutionarily-related to plastids, see if it has plant-like metabolic pathways or other targets that plant (and chloroplast)-specific drugs would act upon. And indeed, what was found that the Apicomplexa possess a non-MVA pathway for isoprenoid biosynthesis, that this pathway is apicoplast-associated, and that drugs that inhibit the non-MVA pathway inhibit the growth of parasites such as P. falciparum. As one early report summarized:

“Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs.

Jomaa H, Wiesner J, Sanderbrand S, Altincicek B, Weidemeyer C, Hintz M, Turbachova I, Eberl M, Zeidler J, Lichtenthaler HK, Soldati D, Beck E.

Institute of Biochemistry, Academic Hospital Centre, Justus-Liebig-University, Friedrichstrasse 24, D-35392 Giessen, Germany. [Enable javascript to see this email address.]

A mevalonate-independent pathway of isoprenoid biosynthesis present in Plasmodium falciparum was shown to represent an effective target for chemotherapy of malaria. This pathway includes 1-deoxy-D-xylulose 5-phosphate (DOXP) as a key metabolite. The presence of two genes encoding the enzymes DOXP synthase and DOXP reductoisomerase suggests that isoprenoid biosynthesis in P. falciparum depends on the DOXP pathway. This pathway is probably located in the apicoplast. The recombinant P. falciparum DOXP reductoisomerase was inhibited by fosmidomycin and its derivative, FR-900098. Both drugs suppressed the in vitro growth of multidrug-resistant P. falciparum strains. After therapy with these drugs, mice infected with the rodent malaria parasite P. vinckei were cured.”

It must be emphasized that, without the evolutionary connection, people would likely not have thought of looking for non-mevalonate isoprenoid pathways in Plasmodium. This pathway is chloroplast-localized in higher plants and is not known in animals. Without the evolutionary link, there is little chance of pulling this pathway “out of the hat”, as opposed to any of the hundreds of other pathways one has to choose from.

The abstracts I post here are relatively old; readers are encouraged to google terms such as “fosmidomycin” to see how fruitful this avenue of evolutionary reasoning has been. (They will find that I have omitted other examples of such reasoning; for example, the apicoplast also houses a prokaryotic fatty acid synthesizing system, and drugs that target this are also promising anti-malarials.) What I hope readers will appreciate is how a decidedly evolutionary line of reasoning has opened the door to a new generation of anti-malarial drugs. Far from being an arcane and irrelevant plaything of biologists, evolution sits at the very heart of this field of experimental biology and medicine. Without the evolutionary connection, there would be no links between isoprenoid biosynthesis in plants and malaria (or between prokaryotic fatty acid biosynthesis and malaria, for that matter). In other words, when ID antievolutionists assert (as Skell does) that evolutionary biology “offers no help to the experimenter–who is concerned, for example, with the goal of finding or synthesizing a new antibiotic, or how it can disable a disease-producing organism”, recall this essay, and think about how badly misinformed Skell and his ilk are.

The citations for the abstracts mentioned above:

Sabine Köhler, Charles F. Delwiche, Paul W. Denny, Lewis G. Tilney, Paul Webster, R. J. M. Wilson, Jeffrey D. Palmer, David S. Roos. A Plastid of Probable Green Algal Origin in Apicomplexan Parasites. 1997. Science 275, 1485-1489. DOI: 10.1126/science.275.5305.1485

Hassan Jomaa, Jochen Wiesner, Silke Sanderbrand, Boran Altincicek, Claus Weidemeyer, Martin Hintz, Ivana Türbachova, Matthias Eberl, Johannes Zeidler, Hartmut K. Lichtenthaler, Dominique Soldati, Ewald Beck. 1999. Inhibitors of the Nonmevalonate Pathway of Isoprenoid Biosynthesis as Antimalarial Drugs. Science 285, 1573-1576. DOI: 10.1126/science.285.5433.1573

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This page contains a single entry by Arthur Hunt published on February 28, 2009 10:15 AM.

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