What do a Japanese golf course and an ancient Chinese remedy have in common? Not much, until the announcement of the 2015 Nobel prizes. Each was the source of parasite-killing drugs that have saved countless lives in some of the poorest countries of the world. They also delivered the Nobel prize in medicine or physiology to their discoverers: Satoshi Ōmura, William Campbell and Youyou Tu.
Thanks to this year’s winners, river blindness and lymphatic filariasis are all but wiped out. And millions have been spared from malaria.
When it comes to Nobels, rewarding the discovery of life-saving drugs is a rarity. In the 114-year history of the prize, only a few have been handed out – the last in 1952 for the discovery of the antibiotic streptomycin from the bacterium Streptomyces griseus. Penicillin, from the furry white Penicillium mould that coats bread and cantaloupes, won the prize in 1945.
As these prizes attest, the natural world is a time-honoured source of medicines. In the arms race to protect themselves against infection, microbes, plants and animals evolved potent chemical weaponry, and folk medicine has long exploited their properties.
This year’s laureates depict the different paths drug discovery can take: one involved a partnership with US pharmaceutical powerhouse Merck, while the other drew on traditional Chinese medicine.
The story behind one half of the prize begins in the 1970s. Japanese microbiologist Satoshi Ōmura, who specialised in looking for new antibiotics, took a close look at the soil-dwelling bacteria Streptomyces – the same group that delivered streptomycin. From a handful of dirt dug up near a golf course in Ito, he isolated thousands of bacteria and grew them in broths, using unique methods he developed himself, before whittling them down to the 50 or so he deemed most promising.
Omura then sent these broths across the Pacific to the US Merck laboratories. There, Irish-born biologist William Campbell fed the broths to mice infected with roundworms. One of the broths cleared the parasite. Campbell isolated the roundworm-snuffing compound, then tweaked its chemical structure to make it extra lethal. He dubbed this new drug ivermectin.
Human trials showed ivermectin successfully treats a host of debilitating and deadly diseases caused by roundworm, including river blindness and lymphatic filariasis (also called elephantiasis). While adult parasites are untouched, it kills the young parasites that cause the debilitating symptoms, though even after decades of use, scientists aren’t sure exactly how the drug works. Unable to reproduce, the adult roundworm eventually dies (typically after two years). As of 2012, ivermectin was administered to more than 200 million people, along with countless livestock and pets – an achievement that delivered Ōmura and Campbell one half of the $960,000 prize.
The second half of the prize took a very different route. Its origins lie in the Chinese Cultural Revolution of the 1960s. Medical researcher Youyou Tu, then leading a group at the Academy of Traditional Chinese Medicine in Beijing, was given a secret military project by Chairman Mao himself: find a cure for malaria, which was ravaging North Vietnamese soldiers fighting the communist cause in jungles south of China.
So Tu pored over traditional Chinese recipes to treat fever. One plant, she noticed, appeared in hundreds of recipes: Artemisia annua, or sweet wormwood.
She boiled up an extract from the plant, and gave it to malaria-infected rats. But the results were inconsistent, with cure rates swinging from 12% to 40%. Had she gotten the recipe wrong?
So she looked back at the literature – and had a ‘Eureka!’ moment. A recipe more than 1,600 years old said the healing juice was squeezed from fresh – not boiled – sweet wormwood leaves.
Cold extraction did the trick. It cured 100% of malaria-infected mice and monkeys. Clinical tests in the 1980s showed the extract not only reduced fever in infected humans, but also dropped the parasitic load in their blood.
Tu refined the active component, known as artemisinin or qinghaosu. It disrupts the ability of the parasite to multiply but as with avermectin, its exact mechanism remains unknown.
While some malaria strains have evolved resistance to artemisinin, it’s still highly effective when used with other drugs and mosquito-control methods such as nets and insecticides.
Will this year’s award inspire researchers to look to nature for medical solutions in an increasingly drug-resistant world?
Matthew Todd, a chemist at the University of Sydney, thinks so: “Every single organic chemist is a bit of a green-blooded hippy in terms of wanting the rainforests to survive. We know there are these compounds in there that are just stunning, and we never want to lose them as a resource.”
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