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Natural Products Research in South Africa: 1890–2010

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Natural Products Research in South Africa: 1890–2010 Page 1 of 8 Review Article Natural products research in South Africa: 1890–2010 Author: Having spent some 50 years as an organic chemist with an interest in medicinal plant 1 Siegfried E. Drewes chemistry in South Africa it was relevant now to ask three questions, (1) when were natural products first utilised, (2) who were the people involved, and (3) what is the status quo? Based Affiliation: 1School of Chemistry, on older literature published in the South African Journal of Chemistry, information gleaned University of KwaZulu-Natal, from attendance at innumerable chemistry conferences, and relevant literature in university Pietermaritzburg, archives, a great deal of information was gathered to answer the first two questions. For South Africa example, that the first veterinarian to treat cattle diseases caused by poisonous plants in the Correspondence to: Eastern Cape was Dr Jotella Soga in the 1890s. Contributions from other prominent scientists Siegfried Drewes such as Marais, Rindl, Rimington and Warren followed. From about 1940 to the 1990s, researchers concentrated mainly on the isolation of new compounds from local plants for Email: which some indigenous knowledge was recorded. Foreign chemists also arrived and did a fair [email protected] amount of ‘exploitation’ of natural products. Thus, the anti-cancer compound combretastatin Postal address: was first isolated from the indigenous tree Combretum caffrum. Plant chemistry in South School of Chemistry, Africa has blossomed in the last decade, with many students from previously disadvantaged University of KwaZulu-Natal, backgrounds, but with a keen interest in muti or medicinal chemistry, entering the field. Scottsville 3209, South Africa Recent findings have rekindled the belief that a major development in natural products would Dates: at last emerge from Africa. Received: 17 May 2011 Accepted: 01 Dec. 2011 Published: 04 May 2012 Introduction How to cite this article: Natural products are compounds synthesised in nature. In this review, natural compounds are Drewes SE. Natural products research in South restricted to those produced by plants. All plants and animals produce primary metabolites Africa: 1890–2010. S Afr (nucleic acids, proteins, sugars and fats) which are used for energy purposes. However, plants J Sci. 2012;108(5/6), Art. also produce secondary metabolites, which are not essential for the life of the plant but serve #765, 8 pages. http:// dx.doi.org/10.4102/sajs. other useful purposes for the plant. For example, some plants exude poisons to keep predators v108i5/6.765 away, others deck themselves in bright colours to attract insects for pollination, whilst others (fortuitously) generate compounds which can be used to treat or cure human ailments, such as malaria, bronchitis and cancer. To date, about 50% of all commercial medicines (drugs) are derived either directly from plants, or are modifications of plant products. Friedrich Wöhler, a prominent organic chemist (and natural products researcher), wrote in 18351: Organic chemistry just now is enough to drive one mad. It gives the impression of a primeval tropical forest, full of most remarkable things, a monstrous and boundless thicket, with no way to escape, into which one may well dread to enter. Researchers are thus challenged to find treatments for HIV/AIDS and other fatal diseases, amongst the indigenous medicinal plants of South Africa. South African researchers have taken up this challenge in a vigorous fashion. Early South African researchers: 1895–1949 Southern Africa is home to over 30 000 species of higher plants and three of the richest floristic regions in Africa, the so-called ‘hot spots’: the Cape Floristic Region, the Maputaland-Pondoland Region and the Succulent Karoo Region. There are also several smaller regions rich in plants. It is reported that 35 000 – 70 000 tonnes of plant material are consumed in South Africa each year, so it is no wonder then that some plants are close to extinction. South Africa’s indigenous plants are not only used for decorative (e.g. proteas) and commercial (e.g. black stinkwood and tamboti furniture) purposes, but about 3000 species are also used as © 2012. The Authors. medicines, mostly by traditional healers. The use of natural products for medicinal purposes Licensee: AOSIS took shape in the late 1800s and early 1900s. At this time, two ‘industries’ were the mainstay of OpenJournals. This work economic growth in South Africa: gold, which had been discovered on the Witwatersrand in is licensed under the Creative Commons 1884, and agriculture – in the form of maize, wheat and related products, together with extensive Attribution License. stock farming. Stock farming was plagued by severe stock diseases which led to the deaths of http://www.sajs.co.za S Afr J Sci 2012; 108(5/6) Page 2 of 8 Review Article thousands of cattle and sheep between 1890 and 1929. Poisonous plants grazed by the animals gave rise to diseases with very descriptive names such as slangkop poisoning (caused by Scilla natalensis and related Scilla species), stywe siekte (caused by Crotolaria burkeana), geel dikkop (caused by ingestion of devil’s claw, Tribulus terrestris) and vermeersiekte (caused by ingestion of the plant Geigeria aspera). Geigeria aspera led to the death of a million sheep in 1929. The impact of these diseases, coupled with the earlier rinderpest epidemic (in the late 1890s) which not only killed cattle and sheep but also decimated veld animals such as buffalo, giraffe, eland and kudu, placed a great strain on veterinarians and medical personnel. The saying ’cometh the time, cometh the man’ was never truer than during those trying years. Real pioneers in the field who were trying to establish the chemistry of the poisons causing all these diseases were, amongst others, Dr D. Hutcheon2, Sir Arnold Theiler3, Dr M. Rindl4, Dr C. Rimington and Dr J. Roets5. Special mention must be made of Dr J.S.C. Marais6 who solved the mystery of the gifblaar (‘poison leaf’, Dichapetalum cymosum), which is highly toxic to sheep, with an LD50 of between 0.25 mg/kg and 0.50 mg/kg. Marais isolated the toxic component in D. cymosum – monofluoroacetic acid (CH2FCO2H), which was the first record of a fluorinated compound found in nature. All of these researchers were from the Onderstepoort Veterinary Research Institute and were responsible for this Source: Photograph courtesy of Professor J. Michael Institute becoming known worldwide. FIGURE 1: Professor Guido Perold. One of the last remaining mysteries of this era was the active component in Geigeria aspera which caused vermeersiekte. The active component was discovered by Professor Guido Perold7 in 1957 (Figure 1). Perold was then at the National Chemical Research Laboratory (NCRL) of the Council for Scientific and Industrial Research (CSIR), and the work that led to the discovery was done in collaboration with colleagues from Imperial College London. Much of this early work appears in the monograph of Professor D.G. Steyn8 and was further reviewed by Mullholland and Drewes9. At the same time as these early researchers were busy with their work, Dr Jotello Festiri Soga, the son of Rev. Tiyo Soga, was quietly applying his medical and indigenous knowledge to help rural farmers in the Eastern Cape combat cattle diseases rife in that area. Dr Soga obtained his degree at the College of Veterinary Medicine at the University of Edinburgh in 1886 and was the first Black South African veterinary surgeon. The bust of Dr Soga (Figure 2) today has pride of place in the garden at the Onderstepoort Veterinary Institute. The turn of the ‘stalwarts’: 1950–1990 The era between 1950 and 1990 was one in which natural products research changed drastically. No longer were chemical structures unravelled largely by degradation Source: Onderstepoort followed by the laborious linking together of the pieces; this FIGURE 2: Bust of Dr Jotello Festiri Soga. http://www.sajs.co.za S Afr J Sci 2012; 108(5/6) Page 3 of 8 Review Article period witnessed terms such as ‘nuclear magnetic resonance spectroscopy’, ‘high-resolution mass spectrometry’ and ‘high-pressure liquid chromatography’ become household words. However, other changes in the direction of this research now became obvious. No longer was there the same concern with curing livestock diseases – human health, and methods of maintaining health, took centre stage. With the recognition of HIV/AIDS as a widespread disease in 1981, many Western researchers started re-examining natural products as a possible source to combat the pandemic. Traditional healers also became involved in seeking a ‘natural’ cure, but so far these efforts have come to nothing. Whilst HIV/AIDS has perhaps dominated the scene, natural products have continued to be a fruitful source to alleviate other illnesses which are responsible for the deaths of millions of people, particularly in Africa. These illnesses include malaria, for which Artemisia annua from China has yielded the very valuable artemisinin,10 tuberculosis (which is frequently Source: S.E. Drewes comorbid with HIV) and cancer, for which interesting FIGURE 3: Professor Frank Warren. developments based on a natural product – the indigenous South African Combretum caffrum tree – are underway. The research on natural products undertaken between 1950 and 1990 will be discussed briefly. For the first 20 years of this period the field was dominated by the research groups led by Professor Frank Warren (1941–1965, University of Natal, Pietermaritzburg; Figure 3) and Professor Manie de Waal (Pretoria University). Both research groups concentrated on alkaloids and their mode of action as toxic substances. Another group at the NCRL, under the guidance of Dr Piet Enslin, examined diverse industrial and fundamental applications of natural products, for example, the compound cucurbitacin B. Cucurbitacin B is a livestock poison; it has a very bitter taste and anti-gibberellic activity, that is, it inhibits plant growth and is therefore industrially important.
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