Tuesday, October 6, 2015

Nobel Prize in Physiology or Medicine

Satoshi Ōmura, William C Campbell and Youyou Tu share the Nobel Prize in Physiology or Medicine, 2015 for their work against parasitic infestations

Approximately 2.4 billion people and more than a hundred countries around the world are affected by parasites. Parasitic infestation had become a huge social and economic burden in affected populations than a mere health problem in the latter half of last century. As affected children failed to attend schools and adults failed to go to work, these diseases had been contributing to the vicious cycle of poverty and illness in less developed countries for past many decades. Thanks to the commitment and foresight of a group of scientists utilizing available resources in the best possible way, we have two compounds that made it to the essential drug category at affordable prices all over the world.

Nematodes and Ivermectin
Soil bacteria and their secondary metabolites had been the focus of therapeutic research from time immemorial. Japanese researcher Satoshi Ōmura isolated around fifty species of bacteria from a local golf course in Shizuoka Perfecture, Japan. A golfer himself, Ōmura attributes his instincts to collect soil from the golf course to his love for the sport. Out of these, one species which proved to be unknown till then was Streptomyces avermitilis. After meticulous cultures and experimentations, he deduced that secondary metabolites from these cultures completely cleared nematodes in experimental mice. Collaborating with William Cecil Campbell of Merck Institute of Therapeutic Research, New Jersey, he isolated the active secondary metabolite Avermectin. On further studies by Campbell, the compound was purified. Its structure was deciphered and pharmacodynamic and pharmacokinetic properties were elucidated. A hydrogenated derivative of Avermectin, called Ivermectin was found to have greater potency, bioavailability and less adverse effects. In 1981, after successful clinical trials, Merck marketed this drug against nematode infestations. For the past three decades and a half, this drug had been effectively used for treating some of the most insidious and intractable tropical parasitic infestations like Onchocerciasis, Strongyloidosis, Ascariasis and Filariasis to name a few.
Satoshi Ōmura who was overjoyed to know his achievement yesterday emphasized the need for us to go back to nature for productive research. He is still a very active researcher with more than five hundred publications to his credit. Currently, he serves as Professor Emeritus of Biochemistry and Chemistry at Kitasato University, Tokyo.
William C Campbell, a biochemist and parasitologist by training and profession has retired from his productive career at Merck Institute of Therapeutic Research and is currently a Research Fellow Emeritus at Drew University, New Jersey, USA. He expressed his utter disbelief when a representative of Nobel Assembly called him to inform his achievement. “You must be kidding”, was his reaction. He emphasized the tremendous team work behind materialization of the drug and dedicated the Prize to the whole Merck research team.

Malaria and Artemisnin
Malaria is a fatal parasitic infestation if not treated effectively. With malarial parasite Plasmodium getting more and more resistant to quinine and chloroquine, the standard choices of treatment, the dire need for newer modes of treatment was increasing. Youyou Tu, formally trained in Chinese traditional medicine and a product of Chinese Cultural Revolution, got involved in antimalarial research in 1969. Her team studied more than 2000 herbs for potential antimicrobial properties. The most efficacious among them was the extract from the herb Artemisia annua. But unfortunately, the adverse effects of this extract were huge in in vivo experiments. Referring an ancient text of Chinese traditional medicine A Handbook of Prescriptions for Emergencies A Handbook of Prescriptions for Emergencies dated 350AD by Alchemist Ge Hong which recommended “a handful of ginghao immersed in two litres of water, wring out the juice and drink it all”, she isolated and purified the active principle Artemisnin. This proved to be a very effective antimalarial agent with least side effects and good bioavailability. The results were published in Chinese Medical Journal in 1979. Novartis collaborated with her team to market the drug globally and since 1990 Artemisnin and its derivatives save the lives of millions affected by malaria around the world. It is manufactured semisyntetically, still relying on mass cultures of the herb and modified for better pharmacogenic properties.
Youyou Tu has worked as a researcher in many institutions including Peking University and Academy of Chinese Medicine. But she was not known to many in China or abroad until yesterday when she was awarded the Prize. She is known as the Professor of three Nos- she has no postgraduate degree, no research experience in world class institutions and no membership in any Academy of Sciences in China or abroad. She now leads a retired life with her family in Beijing, China.

Interesting facts
It is very interesting to know that none of the scientists involved in the research of these two antiparasitic drugs holds the patent for these compounds. As these compounds were discovered and found to be potentially marketable, the research teams gave the rights to Merck and Novartis to manufacture the drug in large scale and meet the global demand. This was the prime reason why these drugs became globally available at affordable prices thus making them to the list of essential drugs worldwide. It is also commendable that since 1987 Merck has been supplying Ivermectin free of cost to more than 100 nations badly affected by river blindness (Onchocerciasis) which is the second most common cause of blindness due to infection. 
The Prize was awarded to two works. One half of the Prize goes to Ōmura and Campbell for their contributions in Ivermectin discovery and the other half goes to Youyou Tu for her efforts in the discovery of Artemisnin and its derivatives. Both works involved utilizing natural secondary metabolites. This may be a call for scientists worldwide to go back to nature for answering the unsolved puzzles hovering above us.
All the publications of Youyou Tu except a few recent ones in Nature, were published in Chinese. The Nobel Assembly had to translate and transcribe her works to assess their depth and significance. 
During the press conference declaring the Prizes, a curious Indian journalist asked the Assembly representatives if this meant acceptance of eastern traditional medicine by the west. The Assembly emphasized that modern research can be inspired by traditional medicine as that system has stood the tests of time over centuries. But it was the efforts of researchers to extract the active principles from these medicines, elucidate their properties and bring these compounds to the market accessible and affordable to the global community that needs acceptance and acknowledgement. Well, that gives Indian scientists working on Ayurveda inspired research, room to think wider and bigger.

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