Readers and colleagues often ask why scientists care to blog, especially given increasing time demands and decreasing research funding. For me, the blog is an opportunity to have discussions with colleagues from diverse research areas all around the world. Quite often, I learn something quite new that I would not normally encounter in my chosen field of cancer pharmacology.
A case in point stems from a reader comment by Dr Italo MR Guedes, a Brazilian soil scientist who writes the blog, Geófagos (Google Translate works well enough unless, of course, you are already fluent in Portuguese). Italo commented on our post about a French research group’s studies on the rationale underlying Ugandan chimpanzee behavior of eating clay soils prior to their favorite plant. The researchers found that the combination of soil and the plant, Trichilia rubescens, led to activation of the plant’s antimalarial compounds (nice copyrighted photograph here by the husband of the primary author).
Italo tells us that his read of the paper leads him to think that the minerals in the soil might directly catalyze the non-enzymatic chemical conversions of T. rubescens compounds to those with in vitro antimalarial activity. I had originally postulated that the clay might improve the bioavailability of antimalarial compounds already present in the plant or contain microorganisms that catalyzed the activation of prodrugs. But Italo’s suggestion of catalysis by immobilized cations in the clay is quite plausible in that platinum catalysts are used commonly in synthetic organic chemistry and daily by those of us who commute in automobiles outfitted with catalytic converters.
What was even more interesting in Italo’s comment was his allusion to the study of clay-mediated, non-enzymatic polymerization of RNA oligomers – a phenomenon I had not heard of previously (or was sleeping through in college biology or chemistry). However, chemist Dr James Ferris and his
former student colleague, Dr Gözen Ertem, performed work in the early 1990s at Rensselaer Polytechnic Institute (RPI) to show that a specific type of clay, montmorillonite, was capable of catalyzing this reaction (1992 Science PDF here).
Correction (13 October 2011): We deeply apologize to Dr. Ertem for mischaracterizing him as a student of Dr. Ferris. Dr. Ertem has informed us that he was a visiting professor in the Ferris laboratory for over 12 years working on RNA and montmorillonite catalysis.
Ferris and Ertem’s work addresses a crucial question in the origin of life on Earth: how could RNA polymers haved formed in the first place, in the absence of RNA polymerase enzymes? Their work on the prebiotic synthesis of RNA polymers on a clay mineral catalyst was discussed by Tim Tyler on talk.origins back in 2003, following a New Scientist article describing work of Jack Szostak’s group on montmorillonite also facilitating the formation of membrane-filled fluid vesicles from fatty acids.
For background, the RNA world hypothesis is based on the fact that RNA carries genetic information (like DNA) but also has enzymatic activity (like proteins: ribozymes – 1989 Nobel Prize in Chemistry to Altman and Cech). Not only can certain RNAs self-splice, but Zhang and Cech went on to show that some RNAs can catalyze the formation of peptide bonds.
RNA bases begin as amino acids (such as aspartic acid, glutamine, and glycine in purine synthesis, plus formate and bicarbonate). Glycine and aspartic acid were among the amino acids shown by the recently-departed Dr Stanley Miller to be formed in his famed experimental system resembling the primordial atmosphere of methane, ammonia, water, and hydrogen, with electrical discharge to mimic lightning (the original 1953 Science paper is a gem, especially when considering Miller was a 23-year-old graduate student at the time – Download PDF here).
Dr Ferris published a nice, free text overview of his group’s work in 2006. This review provides an elegant and approachable treatise on the chemistry of the origins of life and discusses how other biological precursors could have been provided from comets and meteorites. Ferris also describes how purines and pyrimidines could have been formed from HCN in the primordial biosphere as opposed to how we make them from amino acids. I hesitate to say it but I’m surprised that the ID movement hasn’t twisted these examples to justify Genesis 3:19 – “For dust thou art; and unto dust shalt thou return.”
So, while I use Terra Sigillata here as a metaphor for medicines derived from the Earth, little did I know that a related clay is implicated in the very origins of life.
Ferris, J.P., Ertem, G. (1992). Oligomerization of Ribonucleotides on Montmorillonite: Reaction of the 5′-Phosphorimidazolide of Adenosine. Science, 256, 1387-1389.
Hanczyc, M.M. (2003). Experimental Models of Primitive Cellular Compartments: Encapsulation, Growth, and Division. Science, 302(5645), 618-622. DOI: 10.1126/science.1089904
Ferris, J.P. (2006). Montmorillonite-catalysed formation of RNA oligomers: the possible role of catalysis in the origins of life. Philosophical Transactions of the Royal Society B: Biological Sciences, 361(1474), 1777-1786. DOI: 10.1098/rstb.2006.1903