The 2015 Nobel Prize-Recognizing the Global Impact of Science

On October 5th, 2015 the Nobel Prize for Physiology or Medicine was awarded to William C. Campbell and Satoshi Omura for “their discoveries concerning a novel therapy against infections caused by roundworm parasites” and awarded to Youyou Tu for “her discoveries concerning a novel therapy against Malaria”. These three scientists were instrumental in identifying the compounds now used as standard of care for many parasitic diseases.

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The winners of the Nobel Prize in Physiology or Medicine. Picture from nobelprize.org

What is the Nobel Prize?

 The first Nobel Prize was awarded in 1901 after Alfred Nobel, most known for inventing dynamite, in 1895 left most of his fortune to a series of prizes in the fields of physics, chemistry, physiology or medicine, literature, and peace. Since then a prize is awarded each year for each field listed above, as well as economic science (starting in 1968). Each recipient of the Nobel Prize receives a Nobel Diploma, a Nobel Medal, and 8 million Swedish kronor (about 1 million US dollars). When given to multiple people in the same field the money is split as determined by the Nobel Prize Committee. It can often take decades for the impacts of scientific discovery to be realized and, therefore, the scientists behind

these important discoveries are often recognized by the Nobel Prize committee decades after their initial discovery.

The 2015 Nobel Prize in Physiology or Medicine:

Parasitic diseases are a global health issue. These diseases such as malaria and roundworm normally affect the poorest populations and can have devastating effects such as blindness and even death when not treated properly. Parasitic worms, such as roundworm, which causes River Blindness and Lymphatic Filariasis, the most common of which is called Elephantiasis, for example are estimated to afflict one third of the world’s population and are particularly prevalent in sub-Saharan Africa, South Asia, and Central and South America.

Malaria, the most common parasitic disease, is a mosquito-borne disease that is caused by a parasite that invades red blood cells, causing fever and possibly death. More than 3.4 billion of the world’s population lives in areas at risk of malaria transmission and each year 450,000 people die from Malaria worldwide. Therefore, finding effective treatment for these parasitic diseases is a great advance in global health.

Who are the people behind the science?

-William C. Campbell is originally from Ireland where he received his undergraduate degree in 1952. He received a PhD from University of Wisconsin in 1957. Campbell worked for Merck Institute for Therapeutic Research most of his career. He is currently a Research Fellow Emeritus at Drew University.

-Satoshi Omura is from Japan where he received his two PhDs in Pharmaceutical Sciences and Chemistry in 1968 and 1970 respectively. He research career was spent at the Kitasato Institute and as a professor at Kitasato University. Currently he is a professor Emeritus.

-Youyou Tu is from China and graduated from the Pharmacy Department at Beijing Medical University in 1955. She has been a Professor at the China Academy of Traditional Chinese Medicine since 1965.

What did they discover? 

The chemical structure of Avermectin and Ivermectin. Picture from nobelprize.org
The chemical structure of Avermectin and Ivermectin. Picture from nobelprize.org

Together William C. Campbell and Satoshi Omura collaborated to discover the drug Avermectin, which treats River Blindness and Lymphatic Filariasis causes by parasitic worms called roundworms. After the initial discovery, Avermectin was later modified to be a more effective compound called Ivermectin. While the mechanism of action of Ivermectin is not known in detail, it is thought to work by inhibiting glutamate-gated chloride ion channels (Campbell et al.,1983) and GABA-activated chloride channels (Wang and Pong, 1982) in invertebrate muscle and nerve cells of the microfilaria, the early stage in the life cycle of parasites. These specific receptors are present in the central nervous system of mammals but have low affinity for Ivermectin and are protected by the blood brain barrier.

Satoshi Omura, while working in Japan, isolated the natural product that became the drug Avermectin from bacteria called Streptomyces, which lives in the soil, while Campbell explored the efficacy of the natural products isolated by Omura, one of which became Avermectin. Avermectin has more recently been shown to have efficacy against other parasitic diseases in addition to roundworm.

A schematic of the process by which Youyou Tu discovered Artemisinin. Picture from nobelprize.org
A schematic of the process by which Youyou Tu discovered Artemisinin. Picture from nobelprize.org

Youyou Tu on the other hand isolated a compound from a plant and showed that it was effective at killing Malaria. In the late 1960s, Malaria was on the rise, as efforts to eradicate the disease were not working. To help address this problem, Youyou Tu, working as part of a large national project in China, turned to traditional Chinese herbal medicine to find a treatment for malaria. Tu employed a large-scale screen of herbal medicine in Malaria-infected animals and identified promising results from the extract of a plant called Artemisia annua. Tu then turned to ancient Chinese literature to help determine how to efficiently extract the active component from Artemisia annua. She was then the first to show the component, now called Artemisinin, was highly effective at killing the Malaria parasite. Artemisinin is able to kill the Malaria parasite early in its development, which makes it an invaluable treatment option. Although the mechanism of action of Artemisinin is not entirely known, evidence suggests the Kelch 13 protein, which is important in the cell cycle, is involved. Mutations in the Kelch 13 protein are associated with delayed parasite clearance and believed to account for the emergence of Artemisinin resistance (Ariey, 2014).

What impact have their discoveries had on Global Health?

Through their work, Campbell, Omura, and Tu have revolutionized how parasitic diseases are treated worldwide. Ivermectin the derivative of Avermectin, is used around the world. It is highly effective against a range of parasites, has limited side effects, and is easily accessible. Treatment with this drug is so successful that River Blindness and Lymphatic Filariasis are on the verge of eradication, which would be a major accomplishment for global health. Similarly, Artemisinin, which Tu isolated and determined is an effective Malaria treatment, is used all over the world in combination treatment with other Malaria drugs. It is estimated to reduce mortality from Malaria by more than 20% overall and by more than 30% in children (Dondrop et al., 2010). For example, this means that over 100,000 lives are saved each year in Africa alone. Artemisinin based therapy has helped the overall global death toll from malaria decline by 50% during the last 15 years (WHO, 2015). Together, the work of these three scientists have saved millions of lives and helped improves the lives of many million more. The 2015 Nobel Prize in Physiology or Medicine is another example of scientific discoveries making an impact worldwide.

References:

Campbell, W.C., Fisher, M.H., Stapley, E.O., Albers-Schönberg, G., Jacob, T.A. Ivermectin: A potent new antiparasitic agent. Science 221(4613):823-828, 1983.

Wang, C.C., Pong, S.S. Actions of avermectin B1a on GABA nerves. Prog Clin Biol Res. 97:373-395, 1982

Ariey, F., Witkowski, B., Amaratunga, C., et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505(7481):50-55, 2014.

Dondorp, A.M., Fanello, C.I., Hendriksen, I.C., et al. AQUAMAT group. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet 376(9753):1647-1657, 2010.

World Malaria Report 2014. ISBN 978 92 4 156483

For more information please visit:

Original Scientific Articles:

Burg et al., Antimicrobial Agents and Chemotherapy (1979) 15:361-367.

Egerton et al., Antimicrobial Agents and Chemotherapy (1979) 15:372-378.

Tu et al., Yao Xue Xue Bao (1981) 16, 366-370 (Chinese)

Nobel Prize in Physiology or Medicine Information:

http://www.nobelprize.org/nobel_prizes/medicine/laureates/2015/press.html

Editor: Kimberly Maxfield

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