The Quest for Cinchona: A Phylogenetic Approach to Understanding the Evolution, Natural Variation and Discovery of Cinchona Bark for the Treatment of Malaria

Carla Brenda Maldonado Goyzueta

Abstract

Quinine, the most famous alkaloid contained in the bark of Cinchona trees, was the main
treatment of malaria for several hundred years, and its discovery provides one of the most
exciting tales in human history. The search for the best quality of Cinchona has been
complicated by several factors such as botanical confusion and great variety in the quantity and
composition of different quinine type alkaloids between species and populations across the
Andes region. However, modern DNA-based species relationships, analytical chemistry, and
bioinformatic tools allows to revisit the evolution and discovery of Cinchona bark and provide
clues to new discoveries of malaria active compounds. The main objectives of the PhD project is
to produce a well-resolved and supported phylogeny of tribe Cinchoneae (Rubiaceae) to address
various questions within the larger project exploring the Quest for Cinchona such as biodiversity
patterns, diversification, correlation with plant defensive chemistry, biogeography of the Andes,
population genetics, and taxonomy, among others. More than eight months of extensive
fieldwork have been conducted with local collaborators in Bolivia, Colombia, Ecuador and Peru
to collect material of the tribe Cinchoneae. With the results obtained so far, several papers are
emerging, some of them have already been published, and several others are in process. Chapter
1 uses a verified dataset of species distribution records to compare with a public database to
address challenges with using unverified data from public databases. Chapter 2 explores factors
explaining the large within species variation of quinine in Cinchona calisaya. Chapter 3
demonstrates unexpectedly high beta-diversity of root-associated fungal communities in the
Bolivian Andes. Chapter 4 describes a new species of Cinchona with a key to Bolivian Cinchona
species. Chapter 5 uses a dated molecular phylogeny to reconstruct the evolutionary history of
the tribe Cinchoneae. Chapter 6 unravel the effective discovery of Cinchona bark by native
Americans and highlight the contribution of traditional knowledge to unmet medical needs of
today, in a time where traditional knowledge is disappearing faster than biodiversity. Chapter 7
describes the development of an effective grinding device for the grinding of herbal samples
such as Cinchona barks. Chapter 8 describes the development of an analytical chemical method
for quantification of the four major Cinchona alkaloids. Finally, Chapter 9 discusses the
importance of collections in medicinal plant research leading into the future.
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