在《西西河 · 淘客熙熙》网站上看到如下留言： 弗莱明因此没有独享诺奖 于 :2011-09-20 02:40:43 由于 “ 弗莱明既没有提纯，也没有做人体实验 ” ，而是由 Chain 和 Florey 完成的，因此总共三人得奖。 屠的 “ 青蒿素 ” 在临床试验差点因为心脏毒性被毙 , 是山东和云南救了这个药。 ( 这个问题造成了后来山东和云南对屠 “ 首先发现青蒿素 ” 持异议 ) 。看看中药常山，是中医最常用的抗疟药，因为毒性一直无法使用。 Lasker 奖颁给屠是对她贡献的肯定，不过更多在她光环背后的人的故事一样精彩。 事实上， 2009 年的 Lasker 临床奖就做得很好，有关 GLEEVEC 的科学研究，药厂研发和临床试验的代表，一个不拉。 最后于 2011-09-20 05:18:35 改 , 共 1 次 ; http://www.talkcc.com/thread/3560881/3#C3567681 这个提示非常好，因为格列卫和复方蒿甲醚都是瑞士诺华公司开发的药品， 2009 年两个药品的专利发明人 Jürg Zimmermann 和周义清等同时获得欧洲发明人奖，对此比较了解。进而由此留言思考：为什么 2009 年的抗癌药格列卫可以三个人获得拉斯克临床医学奖，而 2011 年的抗疟药青蒿素就只能是一个获奖人？ 首先考虑的是先对比 2009 年和 2011 年获奖项目的介绍，为了让读者了解原文和方便按时间历程进行对比，故只摘录原文，先不翻译，原文比较更加准确。 从写法上看有什么不同？读者由此能得出什么结论，对此的看法又是什么？欢迎探讨。 其实， Lasker 奖的推荐人和委员会更应该给予解释。 格列卫 Gleevec 青蒿素 Artemisinin (Coartem) Lasker~DeBakey Clinical Medical Research Award Brian Druker, Nicholas Lydon, and Charles Sawyers For the development of molecularly-targeted treatments for chronic myeloid leukemia, converting a fatal cancer into a manageable chronic condition. Lasker~DeBakey Clinical Medical Research Award Tu Youyou For the discovery of artemisinin, a drug therapy for malaria that has saved millions of lives across the globe, especially in the developing world. Award Description Award Description 1. In 1960, Peter Nowell and the late David Hungerford, working in Philadelphia, noticed an abnormally small chromosome in cells from patients with CML. 2. Several world-class molecular biology groups then figured out that the Philadelphia chromosome generates an enzyme that promotes aberrant cell division. Although the idea held enormous appeal, many scientists thought it would not work. 3. As these results emerged in the mid 1980s, Druker, who was training to be an oncologist at the Dana-Farber Cancer Institute, and Lydon, a biochemist at Ciba-Geigy (now Novartis) realized that blocking BCR-ABL might obliterate a CML cell's ability to stir trouble. 4. By the early 1980s, the field of oncogenes had implicated unruly kinases in cancer, and Ciba-Geigy had begun to explore these proteins as potential drug targets. Lydon set up the company's tyrosine kinase inhibitor program in 1986, under the direction of Alex Matter. Their team , which included cell biologist Elizabeth Buchdunger and chemist Jürg Zimmermann, was screening large chemical collections for compounds that hamper tyrosine kinases in test tubes and inside cells. 5. They then chemically tweaked promising compounds, hoping to improve potency and selectivity. Along the way, Lydon began using a molecular tool that Druker made while studying kinases in the laboratory of Thomas Roberts (Dana-Farber Cancer Institute). 6. In 1993, Druker set up his own laboratory with a single goal in mind: Find a company that had a BCR-ABL kinase inhibitor and develop it for clinical use in CML patients. He contacted Lydon, who sent several compounds for Druker to test. 7. In 1996, Druker and Lydon reported that one of these substances, imatinib (now widely known as Gleevec), killed cultured cells that required BCR-ABL activity to survive, but did not affect a cell line that depended on a different tyrosine kinase, v-SRC. 8. Ciba-Geigy and Druker assembled a team to design the clinical trials. A key member was Charles Sawyers, who was studying BCR-ABL at the University of California, Los Angeles. To perform the first clinical trials, they enlisted the collaboration of Moshe Talpaz, an oncologist at MD Anderson Cancer Center. 9. But before they could conduct the study, the enterprise hit some bumps. Ciba-Geigy merged with Sandoz to form Novartis, and Lydon left the company soon afterward. Toxicity concerns arose, although Druker thought they could easily be handled in the clinic. Passionate in his belief that Gleevec showed tremendous promise and eager to offer patients a potentially life-saving therapy, he lobbied Novartis to move the project forward. 10. Druker, Sawyers, and Talpaz finally got the go ahead to begin a clinical trial, which started in June 1998. The first study aimed primarily to assess Gleevec's safety in chronic-phase CML patients who had not responded to interferon-based therapy or could not tolerate its side effects. These results were astonishing for a cancer drug. Typically, researchers hoped that about 10-20 percent of patients would respond in a clinical trial; in this study, 98 percent of the patients showed dramatic improvements. 11. In May of 2001, less than three years after the beginning of the first clinical study, the US Food and Drug Administration (FDA) approved the drug. 12. During the 2006 study, the scientists realized that Gleevec, as remarkable as it was, did not "cure" patients in the strictest sense. 13. But another challenge was simmering. Some patients were developing resistance to the drug and Sawyers wanted to figure out why. Initial analysis of the BCR-ABL gene revealed a sequence alteration that caused one amino acid to replace another at a particular spot in the protein. John Kuriyan (University of California, Berkeley) had recently deduced the structure of the BCR-ABL enzyme bound to Gleevec using X-ray crystallography, and the picture he produced explained what Sawyers observed. 14. Sawyers proposed to find agents that block the resistant enzyme's activity by fastening to BCR-ABL's active form, yet barring it from performing its reaction. Sprycel progressed rapidly through clinical trials and is FDA approved for patients with resistance to Gleevec. Scientists are exploring the possibility of treating people with combinations of Gleevec and second-generation medications such as Sprycel, with the hope of delaying or preventing the emergence of drug resistance. 15. Approximately 120,000 CML patients and 28,000 GIST patients are currently being treated with Gleevec worldwide. 16. Druker, Lydon, and Sawyers seized upon the known molecular defect that underlies CML, formulated the idea of tackling this root cause of the disease, crafted a specific kinase inhibitor, and designed a second-generation inhibitor when drug resistance developed. Druker, Lydon, and Sawyers have provided a stunningly successful treatment for CML and a new paradigm for cancer therapy. 1. The first known medical description of Qinghao lies in a 2000-year-old document called "52 Prescriptions" (168 BCE) that had been unearthed from a Mawangdui Han Dynasty tomb. 2. The covert operation, named Project 523 for the day it was announced—May 23, 1967—set out to battle chloroquine-resistant malaria. 3. In early 1969, Tu was appointed head of the Project 523 research group at her institute, where practitioners of traditional medicine worked side by side with modern chemists, pharmacologists, and other scientists. 4. By 1971, her team had made 380 extracts from 200 herbs. 5. At a March 1972 meeting of the Project 523 group's key participants, she reported that the neutral plant extract —number 191—obliterated Plasmodia in the blood of mice and monkeys. Later that year, Tu and her team tested the substance on 21 people with malaria in the Hainan Province, an island off the southern coast of China. 6. On November 8, 1972, she and her colleagues obtained the pure substance. They named it Qinghaosu. Tu and her colleagues subsequently determined that it had an unusual structure. 7. Subsequent clinical trials on 529 malaria cases confirmed that the crystal they had isolated delivers the antimalarial blow. Many scientists from other institutes then joined efforts to improve the extraction procedures and conduct clinical trials. 8. In October 1981, the scientific working group on the chemotherapy of malaria, sponsored by the WHO, the World Bank, and United Nations Development Business, invited Tu to present her findings at its fourth meeting. 9. In 1973, as part of her structural studies, Tu had modified artemisinin to generate a compound called dihydroartemisinin. 10. Starting in the mid 1970s, Guoqiao Li (Guangzhou College of Traditional Chinese Medicine) performed clinical trials with artemisinin and these substances. 11. In 1980, Keith Arnold (Roche Far East Research Foundation, Hong Kong) joined Li's enterprise and two years later, they published the first high-profile clinical trial of artemisinin in a peer-reviewed, western journal. 12. In 2001, the WHO signed an agreement with Novartis, the manufacturer of one of these drug combinations, Coartem; it consists of artemether and lumefantrine, another antimalarial agent, which was originally synthesized by the Academy of Military Medical Sciences in Beijing. The company is supplying the drug at no profit to public health systems of countries where the disease is endemic. To date, Novartis has provided more than 400 million Coartem treatments. by Evelyn Strauss, Ph.D. by Evelyn Strauss, Ph.D. http://www.laskerfoundation.org/awards/2009_c_description.htm http://www.laskerfoundation.org/awards/2011_c_description.htm 请读者再参考 博文《拉斯克奖没有按WHO治疗疟疾规范办事》 http://blog.sciencenet.cn/home.php?mod=spaceuid=396469do=blogid=492494 中信出版社图书《神奇的抗癌药丸》
标签: 格列卫
