F Rosa Rubicondior: Creationism in Crisis - Which Side Should a True-Believing Creationist Be On? The 'Designer' Who Designs Resistance Or The Scientists?

Tuesday 21 November 2023

Creationism in Crisis - Which Side Should a True-Believing Creationist Be On? The 'Designer' Who Designs Resistance Or The Scientists?

Diagram of the complex eukaryote, Plasmodium falciparum
New approaches in the fight against drug resistance in malaria | FAU Erlangen-Nürnberg

Despite asking creationists multiple times how they reconcile believing that their putative intelligent [sic] designer designs complex organisms, such as the parasite, Plasmodium falciparum which cause malaria, with their belief that this putative designer is the supposedly omnibenevolent god if the Bible and Qur'an, I can never get a rational answer.

Most often they resort to the fallback claim that parasites and the suffering they cause were not created by their putative intelligent designer, but by another designer they call 'Sin', which of course is nonsensical and borders on blasphemy because it denies the supremacy of their supposed designer god, and allows for another designer over whom their supposedly omnipotent god is powerless.

But, to their embarrassment, if they manage to do the joined-up thinking, their guru, Michael J. Behe - who has the status of a 'brilliant scientist' in creationist circles - wrote a book, The Edge of Evolution in which he argued (wrongly) that the development of anti-malarial drug resistance in Plasmodium falciparum must have been intelligently designed, using the 'big scary numbers' tactic of arguing that the likelihood of each of the five steps needed arising by chance was so small, that the chances of all five of them occurring in the right sequence is so infinitesimally small that it couldn't have happened by chance alone, so needed divine intervention.

The fact that he used bad biology and even worse maths, in effect assuming that all the mutations had to happen together in as single cell as a single event, instead of in parallel across the species gene pool, as was shown by microbiologist Kenneth R Miller, is by the by, since creationists generally treat anything Michael J Behe says as proven science, they are stuck with his claim that their god is responsible for anti-malarial drug resistance in the malaria parasite - which infects about 20 million people, mostly children annually, and kills 700,000 of them.

Creationists also believe, contrary to the claim that humans have free will, that their god has a plan for each of us, so presumably planned to have those people die of malaria, and that to oppose their god's divine plan in any way is to oppose their god.

So, again a question I can never get a rational response to, is what should a true-believing creationist support - the god whom they believe creates parasites like malaria as part of its divine plan, or the biomedical scientists who work to thwart that plan?

This is of course, the sort of dilemmas that creationists need to avoid rather than have people accept that parasites like Plasmodium falciparum are the result of a mindless, amoral evolutionary process.

By contrast, and devoid of the sort of muddle, holding mutually exclusive views simultaneously, and dilemmas that creationism, with its evidence-free superstitions, gets itself into, the scientific view, supported by evidence, is:
How did the malaria-causing Plasmodium genus evolve? The Plasmodium genus, which includes the parasites responsible for causing malaria in humans, has a complex evolutionary history. Malaria is primarily caused by five species of Plasmodium: P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. These parasites belong to the phylum Apicomplexa, a group of single-celled organisms that includes various other parasitic protists. The evolution of Plasmodium is thought to have occurred over millions of years. Here are some key points in the evolutionary history of the Plasmodium genus:
  1. Divergence from Free-Living Ancestors: The ancestors of Plasmodium were likely free-living, photosynthetic organisms related to algae. The transition from a free-living lifestyle to a parasitic one involved various genetic changes and adaptations to exploit host organisms.
  2. Adaptation to Vertebrate Hosts: The Plasmodium genus evolved the ability to infect vertebrate hosts, including reptiles, birds, and mammals. The specific adaptation to humans is believed to have occurred independently in different Plasmodium species.
  3. Host Switching: Plasmodium species have a history of switching hosts, which has contributed to the diversity of species and their ability to infect different types of animals. For example, P. knowlesi is a malaria parasite that infects macaques but can also infect humans.
  4. 4. Co-Evolution with Hosts: The evolution of Plasmodium is closely linked to the evolution of its hosts. As hosts develop immune responses to combat the infection, Plasmodium evolves mechanisms to evade host defenses. This ongoing co-evolution has led to the diversity of Plasmodium species and their ability to persist in different host environments.
  5. Geographic Distribution: Different Plasmodium species have distinct geographic distributions, reflecting historical patterns of host distribution and movement. For example, P. falciparum is more prevalent in tropical regions, while P. vivax has a wider distribution and can be found in both tropical and temperate zones.
Understanding the evolutionary history of Plasmodium is important for efforts to control and eliminate malaria. It provides insights into the biology of the parasite, its interactions with hosts, and potential vulnerabilities that can be targeted for intervention strategies. Additionally, studying the evolution of drug resistance in Plasmodium populations is crucial for the development of effective antimalarial treatments.

What is the reason for thinking their ancestors 'were likely free-living, photosynthetic organisms related to algae'?

The idea that the ancestors of the malaria-causing Plasmodium parasites were likely free-living, photosynthetic organisms related to algae is based on several lines of evidence, although it's important to note that the precise evolutionary history is not fully resolved, and alternative hypotheses exist.
  1. Phylogenetic Relationships: Molecular phylogenetic studies, which analyze genetic data to infer evolutionary relationships, have suggested that the Apicomplexa, the phylum to which Plasmodium belongs, is closely related to dinoflagellates and other photosynthetic algae. This supports the idea that the common ancestors of Apicomplexa were likely photosynthetic.
  2. Presence of Apicoplast: One of the key features supporting the hypothesis of a photosynthetic ancestry is the presence of a unique organelle called the apicoplast in the Plasmodium genus. The apicoplast is derived from a photosynthetic algal ancestor but has lost its ability to photosynthesize. Instead, it plays essential roles in lipid biosynthesis and other cellular processes. The presence of the apicoplast and its similarities to chloroplasts in algae suggest an evolutionary connection to photosynthetic organisms.
  3. Genome Analyses: Comparative genomics studies have revealed similarities between the genomes of Plasmodium and those of free-living photosynthetic organisms. These similarities include the presence of genes and genetic elements that are typically associated with photosynthetic processes.
  4. Evolutionary Adaptations: The transition from a free-living, photosynthetic lifestyle to a parasitic one is a common evolutionary phenomenon. Many parasitic organisms are believed to have evolved from free-living ancestors as they adapted to exploit host environments for resources.
While these pieces of evidence support the idea of a photosynthetic ancestry for the Plasmodium genus, it's crucial to acknowledge that the evolutionary history of these parasites is complex, and alternative hypotheses exist. Ongoing research and advancements in molecular biology and genomics may provide more insights into the origins of Plasmodium and other related parasites.
before we move on to the substance of this blog - the scientific progress in creating an anti-malarial drug to which the parasites have not evolved resistance (or been intelligently redesigned, as Michael J. Behe insists), let's pause a moment to consider the above account of the evolution of the Plasmodium genus. Creationists will want to ignore the fact that these were once free-living photosynthesising organisms related to the dinoflagellates (with their 'irreducibly complex' flagella © Micharl J. Behe) and that, during their evolution they lost their photosynthetic ability but retained the remnants of their chloroplasts, exapted for a different function, and some of the genes for photosynthesis. Why would a malaria-causing parasite need genes for photosynthesis?

And let's not forget that the chloroplasts in photosynthetic cells are themselves genetically reduced cyanobacteria that formed a symbiotic alliance with other prokaryote cells to form single-celled eukaryote cells in the dim distant past, billions of years before creationists superstition says the Universe was created, by the same 'intelligent [sic] designer they believe created the malaria-causing parasites, complete with their redundant genes for photosynthesis and the remnants of the cyanobacteria they once contained.

Now to the science that should also embarrass creationists:

Biomedical scientists trying to find an effective treatment for malaria are about to give the arms race another twist. Whether this will be the final twist remains to be seen.

What researchers at the Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany, led by Prof. Dr. Svetlana B. Tsogoeva, have done is combine the compound that the parasites have recently become resistant to - artemisinin, derived from the plant wormwood, Artemisia annua - with another plant-derived compound, coumarin. They then combined this with an autofluorescent compound so they could observe the effects on cells. It transpired that the autofluorescent compound was effective against artemisin-resistant Plasmodia.

They have published their findings open access in the journal Chemical Science and is explained in a Friedrich-Alexander-Universität news release:

Artemisinin is a highly-effective and common ingredient for the manufacture of malaria medication gained from a plant called sweet wormwood (Artemisia annua L.). Coumarin is a secondary plant compound found in various plants. In the development of drugs against malaria, active substances are labeled with fluorescent substances in order to identify how they act against malaria pathogens in precise chronological order using imaging techniques. This fluorescent labeling has already been used with artemisinin.

Combining substances to achieve autofluorescence
A significant disadvantage of labeling with fluorescent substances is the fact that they alter how the medication works. For example, this means that in certain circumstances cells infected with malaria absorb a drug like artemisinin differently after fluorescent marking than previously. The solubility of the drug can also change. This was avoided by the development of autofluorescent hybrids, which are compounds made of two or more basic compounds that are inherently fluorescent and whose mode of action can be precisely observed using imaging techniques.

Active agent with special skills
The team led by Prof. Tsogoeva at the Chair of Organic Chemistry I decided to combine artemisinin with bioactive coumarins because coumarin derivatives also possess anti-malaria properties. They can also be easily chemically altered so that they become extremely fluorescent. The researchers discovered that it was not only possible to observe the mode of action of this first autofluorescent artemisinin-coumarin hybrid in living red blood cells infected with P. falciparum. In conjunction with Prof. Barbara Kappes (Department of Chemical and Biological Engineering, FAU) and Dr. Diogo R. M. Moreira (Instituto Gonçalo Moniz, Fiocruz Bahia, Brazil), they also discovered that the active agent was highly effective against P. falciparum strains in vitro (in a test tube) that are resistant to chloroquin and other malaria drugs. Above all, however, the new compound also proved highly effective against the malaria pathogens in vivo in mouse models.

With the creation of the first autofluorescent artemisinin-coumarin hybrid, the FAU researchers hope that they have laid the foundation for the development of further autofluorescent agents for treating malaria and have made significant process in overcoming multi-drug resistance in the treatment of malaria.
More technical details are given in the abstract and introduction to the team's paper in Chemical Science:
Malaria is one of our planet's most widespread and deadliest diseases, and there is an ever-consistent need for new and improved pharmaceuticals. Natural products have been an essential source of hit and lead compounds for drug discovery. Antimalarial drug artemisinin (ART), a highly effective natural product, is an enantiopure sesquiterpene lactone and occurs in Artemisia annua L. The development of improved antimalarial drugs, which are highly potent and at the same time inherently fluorescent is particularly favorable and highly desirable since they can be used for live-cell imaging, avoiding the requirement of the drug's linkage to an external fluorescent label. Herein, we present the first antimalarial autofluorescent artemisinin-coumarin hybrids with high fluorescence quantum yields of up to 0.94 and exhibiting excellent activity in vitro against CQ-resistant and multidrug-resistant P. falciparum strains (IC50 (Dd2) down to 0.5 nM; IC50 (K1) down to 0.3 nM) compared to reference drugs CQ (IC50 (Dd2) 165.3 nM; IC50 (K1) 302.8 nM) and artemisinin (IC50 (Dd2) 11.3 nM; IC50 (K1) 5.4 nM). Furthermore, a clear correlation between in vitro potency and in vivo efficacy of antimalarial autofluorescent hybrids was demonstrated. Moreover, deliberately designed autofluorescent artemisinin-coumarin hybrids, were not only able to overcome drug resistance, they were also of high value in investigating their mode of action via time-dependent imaging resolution in living P. falciparum-infected red blood cells.
Graphical Abstract

Autofluorescent antimalarials by hybridization of artemisinin and coumarin: in vitro/in vivo studies and live-cell imaging
Nature is an excellent source of drugs or their precursors.1 Antimalarial drug artemisinin (Fig. 1a) is a prominent natural product. It is an enantiomerically pure sesquiterpene lactone found in Artemisia annua L. Its discoverer Youyou Tu was awarded the 2015 Nobel Prize in Physiology or Medicine.2,3 Artemisinin and its derivatives are of great interest for their vast range of biological properties.4,5 Target identification experiments have recently been performed, and putative inhibitory mechanisms of artemisinin-related compounds have been studied.68 Notably, one of the most powerful tools to address the mode of action of bioactive compounds is an investigation via fluorescence-based techniques.9,10 A fluorescent non-drug label is commonly introduced into a drug molecule to make it suitable for live-cell fluorescence tracking.11,12 In the past, this approach was also applied to artemisinins.1316 Though fluorescent labeling enables localization imaging, the concept has significant drawbacks. The drug's polarity, solubility, cellular uptake, biological activity, and mode of action can significantly alter as the pristine drugs are heavily altered and enlarged.17,18 One possible pathway to circumnavigate drawbacks accompanied by fluorescent labeling is the design and application of inherently fluorescent bioactive hybrids, which are potent drug compounds and fluorophores at the same time.17,19 The efficacy of hybrid drugs and their potential to overcome even drug resistance has been widely proven.2029 To our knowledge, no examples of inherently fluorescent antimalarial hybrid drugs have been reported so far. The aim of this work is, therefore, to combine two desired features in one artemisinin-based antimalarial hybrid drug: (i) high in vitro/in vivo activity and (ii) high intrinsic fluorescence. To design fluorescent artemisinin-based antimalarial hybrids, an additional bioactive species is required to gain improved antiplasmodial activity and to enable autofluorescence. We selected bioactive coumarins as prominent and suitable pharmacophores. While few examples of anticancer artemisinin-coumarin hybrids are known,3032 no examples of antimalarial artemisinin-coumarin hybrid compounds and their in vitro/in vivo analyses and mode of action studies have been reported to date. Coumarin derivatives e.g., scopoletin, showing antimalarial properties, and other derivates naturally occur with artemisinin in Artemisia annua L.3337 In addition to their antimalarial properties, coumarin derivatives exhibit activities against a broad scope of pathogens3841 and are highly suitable for synthesizing intrinsically fluorescent hybrids since they can be tuned to be strongly fluorescent by binding to a triazole subunit.42,43
Fig. 1 (a) Structures of established antimalarials chloroquine, artemisinin and artesunic acid and their in vitro activity against CQ-resistant and multidrug-resistant P. falciparum strains Dd2 and K1. (b) The first systematic comparison of antimalarial activities of differently linked monomeric and dimeric artemisinin-based hybrid model drugs using in vitro, in vivo and live-cell bioimaging methods.

Lots of things for creationists to throw tantrums or go into abject denialism over in this news:

Firstly, there is the evolution of the Plasmodium genus from free-living, photosynthesising dinoflagellates, complete with the loss of some genes, the retention of some for photosynthesis even though the Plasmodia no longer need them, and the retention and repurposing of the remnants of chloroplasts into 'irreducibly complex' new structures - the apicoplasts.

Then there is the age-old problem of who created these parasites with the apparent purpose of killing hundreds of millions of children annually, and then redesigning them to overcome medical science's attempts to irradicate it.

And last but not least, whose side should devout creationists be on, the god for whom malaria is supposedly part of a plan or the scientists trying to thwart it?

All compounded by Michael J Behe's blunder in pulling the 'Sin did it!' excuse rug from under the feet of creationists by misusing malarial resistance as an example of intelligent [sic] design, and therefore 'proof' that their god is responsible for what looks like evolutionary change, even in parasites. Or do the supposedly monotheist creationists have two creator gods?

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1 comment :

  1. I support scientists to rid the world of malaria. This God certainly isn't going to do it. He just let's His creation suffer and die. And it's all because two primitive humans ate a forbidden apple according to the stupid mythical story in Genesis. Creationists such as Ken Ham, Kent Hovind, Ray Comfort, and Michael J. Behe are woefully delusional.


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