Nobel Prize for Parasite Killers

(October 6th, 2015) The Nobel Prize for Physiology or Medicine 2015 is shared equally by Youyou Tu for discovering the anti-malaria compound artemisinin, and Satoshi Omura and William Campbell for discovering a drug against parasitic worms.





Satoshi Omura’s research specialty has been isolating and systematically scrutinising unknown microorganisms for new drugs. Doing so, he and his team members at the Kitasato University in Tokyo continuously tried out new methods to get pure microbe cultures. At the end of the 1970s, Omura’s team examined a soil sample from a Japanese golf course – and found Streptomyces avermitilis. A bacterium destined for worldwide glory, as it produces the compound Avermectin.

William C. Campbell, an Irish researcher working in the US and back then team leader at the Merck Institute for Therapeutic Research, acquired the promising bacterial culture from Omura and demonstrated the enormous potential of Avermectin for fighting parasitic roundworms. The days of nasty nematodes, such as Onchocerca volvulus, causing river blindness, a dreaded disease in the tropics, were numbered.

Through chemical modifications, Campbell’s lab synthesised the much more potent Ivermectin. This substance is a neurotransmitter antagonist. The drug binds to certain neuronal ion channels (glutamate-gated chloride channels), making the synaptic membrane more permeable for chloride ions. The consequence is muscle paralysis in the parasitic worms. Humans don’t possess this channel type in their peripheral nervous system, which is why Ivermectin specifically kills the parasitic worms. Poisoning roundworms is actually fairly easy. The biggest problem, however, was how to get rid of the eukaryotic parasite without harming the genetically similar host.

In clinical studies, Ivermectin proved its deadly effectiveness: river blindness is almost eradicated today and also the pathogen causing elephantiasis is close to extinction – a loss of biodiversity that, for once, no one is sad about.

The other half of the Nobel Prize honours a discovery that was a huge step forward in the fight against another eukaryotic parasite: at the University of Beijing, Youyou Tu discovered a drug against the protozoon Plasmodium falciparum, the causing agent of malaria.

Tu focussed on extracts of the wormwood plant, Artemisia annua but, in the beginning, her results were not very consistent. In an old script from Traditional Chinese Medicine she eventually found a recipe, which served as inspiration for more experiments. At the end, Tu isolated the compound artemisinin. The drug made from this compound controls malaria fairly well, in combination with other medication. Unfortunately, artemisinin resistance has already developed and new anti-malarials are urgently needed. Maybe this year’s Nobel Prize will fast-track research in this area.

Tu’s high honour is certainly remarkable because this is the first Nobel Prize for a scientist, who extensively studied Traditional Chinese Medicine (TCM). It’s, however, not a Nobel Prize for TCM in general. This was also emphasised by the Nobel Prize committee’s spokesperson in the press conference after the announcement. Traditional herbal medicine was merely the starting point for experiments that finally led to the discovery of a defined drug – which then had to prove itself in “traditionally scientific” clinical studies. 

Four final comments about this year’s Nobel jamboree:
First: It seemed like the Nobel committee finally realised how ridiculous it is that, since 1901, only eleven women received Nobel Prize honours. Last year, it was neuroscientist May-Britt Moser and now YouyouTu: seems like it’s not that hard to find female scientists who deserve their award.

Second: Both Campbell’s and Omura’s first response was something like: it’s impossible to credit this Prize to any one person; it rather belongs to the big teams behind the discoveries. Campbell even said, he thought it was impossible to win the Nobel Prize for Avermectin for exactly that reason as not teams are awarded but three single persons maximum. This is in accordance with Alfred Nobel’s provisions but clearly is no longer suited to this day and age.

Third: Those who think that only publications in the “glam mags”, such as Nature, Science or Cell, can win Nobel Prizes, will rub their eyes in disbelief when looking at the key publications of this year’s Nobel laureates: they were published in community journals, like "Antimicrobial Agents and Chemotherapy" (Impact Factor 4.5) and the Chinese-language local paper "Yao Xue Xue Bao".

Fourth: Finally a real medicine prize again. The Nobel Prize for Physiology or Medicine often (perhaps too often?) honours basic scientists of biology. Alfred Nobel didn’t designate a Prize for Biology. Thus, molecular biology has been put to the categories medicine/physiology or chemistry. That’s alright but this practice is clearly at the expense of “real” medicine. Hence, discoveries like the parasite-killing compounds of this year’s laureates should be just what the founder of the Prize had in mind.

“Alfred Nobel would be happy,” said the chairman of the Nobel Prize committee yesterday.

Hans Zauner (translation: Kathleen Gransalke)

 

This article first appeared in German at www.laborjournal.de

Photo: Ill. N. Elmehed. © Nobel Media AB 2015




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