This year’s Nobel Prize in Physiology or Medicine was announced this morning, and wow! These are awards that the research community (and world) watches very carefully, so there is a lot of buzz around who wins - and who doesn’t.
This year’s prize went to three researchers: William C. Campbell (1/4), Satoshi Ŏmura (1/4), and Youyou Tu (1/2).Campbell and Ŏmura won for their work discovering avermectin to treat roundworm parasites, and Tu won for her work discovering arteminisin to treat malaria. These diseases affect millions of poor individuals, largely in tropical regions.
The roundworm disease, river blindness, has been receiving a lot of attention since President Jimmy Carter announced his wish to see the disease eliminated during his lifetime. This terrible disease is caused by the roundworm Onchocerca volvulus, which is spread through black fly vector. Elimination of this disease is being mediated by distribution of the avermectin derivative, ivermectin. The specificity of avermectins for helminthes over their human hosts is what makes this drug so powerful.
As multicellular infectious agents, discovering a target unique to the roundworm parasite was a challenge. Hygromycin B and Geneticin are aminoglycosides that are block protein synthesis in eukaryotics cells, but toxicity and resistance can be issues in the clinic. Avermectin and its derivatives target glutamate-gated chloride channels, present only in helminthes and some insects. This specificity means there is little toxicity relative to other available drugs.
In 1979, a three-paper series was published in Antimicrobial Agents and Chemotherapy, which described this novel family of antihelmitic agents. Burg, et. al., described the optimal production conditions for avermectin fermentation from Streptomyces avermitilis. Miller, et. al., reported a practical scheme for its isolation. And Egerton, et.al., examined its efficacy in cattle, dogs, chickens, and sheep. Together, these papers introduced a means of mass-producing a powerfully effective drug that has benefited millions of individuals.
Youyou Tu was screening Chinese herbs for antimalarial activity, when she came upon sweet wormwood. The extract from this plant, arteminisin, inhibited plasmodial growth in animals. This too changed the relationship of a parasitic infection affecting millions of people – demand for the drug has led to production of semisynthetic arteminisin in yeast to increase yields.
This Nobel Prize reflects the still-unmet need to address neglected tropical diseases, which affect 1.4 billion people. These diseases primarily affect poor, underdeveloped nations with less scientific and medical infrastructure than wealthier nations. By spotlighting the impact of these researchers, let’s hope the Nobel committee inspires current and future scientists to tackle these important infectious diseases.
-- Julie Wolf