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Sep 14, 2011

2011 Lasker Awards Honor Research on Protein Folding and Development of Artemisinin

  • The Albert and Mary Lasker Foundation has announced the winners of the 2011 Lasker Award: Franz-Ulrich Hartl, M.D., and Arthur L. Horwich, M.D., for basic medical research, Tu Youyou for clinical research, and The Clinical Center of the National Institutes of Health for public service. Lasker Awards, which carry an honorarium of $250,000 for each category, will be presented at a ceremony on Friday, September 23 in New York City.

    Dr. Hartl of the Max Planck Institute of Biochemistry and Dr. Horwich of Yale University School of Medicine will receive the 2011 Albert Lasker Basic Medical Research Award for discovering a cellular machine that controls how newly manufactured proteins fold into their biologically active structures.

    Tu of the China Academy of Chinese Medical Sciences will receive the 2011 Lasker~DeBakey Clinical Medical Research Award for discovering artemisinin, the most effective treatment now available against malaria. The Clinical Center of the NIH will receive the Foundation's Public Service Award for serving as a model institution that has transformed scientific advances into innovative therapies and provided high-quality care to patients.

    "The intellectual skill, vision, and clarity of thought displayed by this year's prizewinners extends the scientific community's understanding of how cells operate, led to new treatments that prevented millions of deaths, and has stemmed human suffering," notes Maria Freire, president of the Lasker Foundation. "Creativity, innovation, and determination have allowed them to pursue novel paths in medical research."

    Additionally, the Mary Woodard Lasker Public Service Award will now be known as "The Lasker~Bloomberg Public Service Award" in honor of Michael R. Bloomberg, philanthropist and mayor of New York City. In naming Bloomberg the recipient of its 2009 Public Service Award, the Foundation cited his willingness to face down fierce opposition from vested interests to reduce tobacco use and promote healthy eating habits, helping to stop disease before it starts.

    "In recognizing the NIH Clinical Center, the Foundation has highlighted the vital role that this research hospital has played in advancing the state of medical research over almost six decades and in training a generation of leaders in biomedical science," remarks Harvey V. Fineberg, chair of the Lasker Public Service Award Selection Committee.

    The 2011 Albert Lasker Basic Medical Research Award honors Dr. Hartl, 54, and Dr. Horwich, 60, for discovering that proteins cannot fold inside cells by themselves. They determined that a protein-dubbed chaperonin because of its assisting role acts as a cage-like folding "machine" that provides a safe place for proteins to fold, away from outside interference.

    The folding process converts linear amino-acid chains into the 3-D forms that determine the molecules' function. Beginning in the late 1950s, scientists thought that newly synthesized proteins in cells folded spontaneously without energy input, as they can in the test tube.

    In the late1980s, Drs. Hartl and Horwich discovered an apparatus that encases an unfolded protein and promotes folding by harnessing the energy of ATP. Once inside this machine, proteins can safely fold without sticking to one other.

    Drs. Hartl and Horwich have shed light on how a previously unknown process involving folding machines isolates young proteins and helps them transform into mature molecules. Subsequent work suggested that protein folding activity may provide therapeutic benefit for such neurodegenerative illnesses as Parkinson disease, Alzheimer disease, Huntington disease, mad cow disease, and amyotrophic lateral sclerosis, which occur when clumps of entangled misfolded proteins cause neurological symptoms.

    The 2011 Lasker~DeBakey Clinical Medical Research Award honors Tu Youyou, 81, for discovering artemisinin. An artemisinin-based drug combination is now the standard regimen for malaria, and the WHO lists artemisinin and related agents in its catalog of "Essential Medicines."

    Tu's seminal work on malaria began when the Chinese government launched a clandestine military project aimed at finding a remedy for the deadly scourge. The operation, dubbed Project 523, for the day it was announced—May 23, 1967—set out to battle chloroquine-resistant malaria.

    In keeping with Chairman Mao Zedong's desire to "explore and further improve" the "great treasure house" of traditional Chinese medicine, Tu combed ancient texts and folk remedies for possible leads. She collected 2,000 recipes, which were then winnowed. By 1971, her team had made 380 extracts from 200 herbs.

    The researchers then assessed whether these substances could clear the malaria-causing parasite from infected mice. One of the extracts from Qinghao—Artemisia annua L., or sweet wormwood—dramatically inhibited parasite growth in the animals. The results were not reproducible, so Tu once again scoured the literature for possible explanations.

    Following clues, she and her team performed the extraction process at low temperatures. Tu's team also removed a harmful acidic portion of the extract that did not contribute to antimalarial activity and refined the preparation of the material in other ways. These innovations boosted potency and slashed toxicity.

    At a March 1972 meeting of the Project 523 group's key participants, she reported that the neutral plant extract wiped out the malaria-causing agent in the blood of mice and monkeys. A pure substance was obtained later that year that proved effective in treating people with malaria.

    The first English-language scientific literature citing successful clinical trials for artemisinin appeared in late 1979, but as was customary in China at the time, the authors were anonymous. The paper drew attention and in 1981, Tu appeared at an international meeting where she presented her findings on artemisinin and its chemical derivatives that form the foundation of today's life-saving therapies.

    The Lasker~Bloomberg Public Service Award honors the Clinical Center of the National Institutes of Health for creating a research hospital where doctors develop innovative therapies and explore new ways to diagnose, treat, and prevent a wide variety of diseases. Research scientists from 18 of the 27 NIH Institutes and Centers collaborate with the Center, which has treated more than 450,000 patients from 149 countries since it opened.


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