This year’s Nobel Prize in Physiology or Medicine recognises the development of antiparasitic drugs and thus also research that has resulted in hundreds of millions of lives being saved and had a major impact on health economics in the world’s poorest countries.
Parasitic diseases have long plagued mankind, and their devastating significance is reflected in the fact that malaria, just one of many parasitic diseases, has been estimated to be the cause of death for half of all the humans who have ever lived (Curr. Med. Chem. 2005, 12, 2539). Despite great advances in modern medicine, more than a third of today’s global population suffers from the consequences of parasitic infections.
While antibiotic research has won Nobel Prizes on several occasions (Gerhard Domagk in 1939 for sulfonamide, Alexander Fleming, Ernst Chain and Howard Flory in 1945 for penicillin, and Selman Waksman in 1952 for streptomycin), this is the first time the discovery of antiparasitic drugs has been recognised. It should, however, be mentioned that Ronald Ross won a Nobel Prize in 1902 for his discovery that malaria is spread by Anopheles mosquitoes, and that Charles Laveran won in 1907 for the revelation that a parasite is responsible for malaria. Their discoveries have thereby laid the theoretical foundations for this year’s prize.
Satoshi Ōmura and William C. Campbell’s discovery of avermectin, a natural product that is isolated from Streptomyces avermitilis and then processed to make the drug ivermectin, has effectively reduced the incidence of elephantiasis (lymphatic filariasis) and river blindness. While elephantiasis causes chronic swelling and oedema, as well as lifelong disability, river blindness causes chronic inflammation of the cornea which can lead to blindness. Like malaria, these parasitic diseases primarily affect the populations of Sub-Saharan Africa, Central and South America and South Asia.
Malaria is caused by single-celled Plasmodium parasites which infect the liver and the red blood cells, resulting in attacks of fever and severe organ damage, and claims almost half a million lives every year. The discovery of artemisinin, a natural product that is isolated from sweet wormwood (Artemisia annua) and then processed to make artemether, which is now used in antimalarial combination drugs, has led to a reduction in death rates from malaria of more than 20%, meaning that more than a hundred thousand lives are saved each year on the African continent alone.
Today’s modern medicine undeniably derives from plant-based medicinal practice in civilisations such as ancient Egypt, China, Greece and Rome. Despite advanced research methods, almost half of all new drugs are still natural products or close derivatives thereof. Certain groups of drugs, such as antimalarial medicines, still consist almost exclusively of natural product derivatives. Consequently, isolating natural products from plants and microorganisms is still a promising route within pharmaceutical research, not least in view of recent estimates that only ten percent of all plants have been analysed phytochemically to date.
There is no doubt that the discoveries of artemisinin and avermectin are of immense significance to mankind. However, the scientific significance of the Nobel Committee’s choice has been interpreted differently and resulted in debate on the use of natural resources in pharmaceutical research and the validity of alternative medicine methods (“Nobel Renews Debate on Chinese Medicine” in the New York Times on 10 October 2015 and “How traditional medicine finally won its Nobel Prize” in Quartz on 6 October 2015, for example).
It is less certain whether this year’s Nobel Prize in Physiology or Medicine will result in any support for the use of alternative medicine treatment methods. Youyou Tu had trawled through a large volume of traditional medicinal notes for high fever cures. Of the almost 2,000 formulations she selected, only one gave a promising – but unreproducible – result: a note by Ge Hong written in the year 340. Inspired by this, she realised something that is usually described as the decisive step in her discovery: the active substance should be extracted through cold extraction to avoid degradation. Following isolation and structure determination, she carried out the first clinical test on herself.
However, artemisinin turned out to have low bioaccessibility and a short half-life, and could therefore not be directly applied as a drug. After Astra, Pharmacia and Kabi had declined further development of the substance in the 1980s, Novartis acquired the rights and developed the combination of artemether (dihydroartemisinin) and lumefantrine – a synthetic quinine derivative – that is currently used to treat malaria. While artemether – which is both more stable and more active than artemisinin itself – kills the parasite quickly during an early stage of its life cycle by inhibiting one of its transport proteins, lumefantrine inhibits the breaking down of haem, the toxic intermediate of haemoglobin breakdown, which induces the formation of free radicals and thereby has a long-term effect which helps to eliminate the remaining parasites.
The extract of Artemisina annua used in natural Chinese medicine is thus not an effective treatment against malaria in itself, even if it has inspired the development of artemisinin-based combination therapies. Without modern pharmaceutical development, artemisinin would never have been able to save millions of lives. Nor should it be forgotten that, of the 2,000 natural medicines for high fever studied by Tu, 1,999 had no antimalarial effect at all. It is therefore clear that this year’s Nobel Prize hardly verifies traditional medicinal treatment methods; rather, it shows that ethnomedicinal experience can assist in the development of modern pharmaceuticals.
It is also interesting to note that Carl Linnaeus reported the use of a decoction of the herb mugwort, Artemisia vulgaris L., to treat tertian fever in 1755.
Mate Erdelyi, Docent, Department of Chemistry and Molecular Biology, University of Gothenburg