Yazdankhah Siamak, Lassen Jørgen, Midtvedt Tore, Solberg Claus Ola
Tidsskr Nor Laegeforen. 2013 Dec 10;133(23-24):2502-7. doi: 10.4045/tidsskr.13.0145.
The development of chemical compounds for the treatment of infectious diseases may be divided into three phases: a) the discovery in the 1600s in South America of alkaloid extracts from the bark of the cinchona tree and from the dried root of the ipecacuanha bush, which proved effective against, respectively, malaria (quinine) and amoebic dysentery (emetine); b) the development of synthetic drugs, which mostly took place in Germany, starting with Paul Ehrlich's (1854-1915) discovery of salvarsan (1909), and crowned with Gerhard Domagk's (1895-1964) discovery of the sulfonamides (1930s); and c) the discovery of antibiotics. The prime example of the latter is the development of penicillin in the late 1920s following a discovery by a solitary research scientist who never worked in a team and never as part of a research programme. It took another ten years or so before drug-quality penicillin was produced, with research now dependent on being conducted in large collaborative teams, frequently between universities and wealthy industrial companies. The search for new antibiotics began in earnest in the latter half of the 1940s and was mostly based on soil microorganisms. Many new antibiotics were discovered in this period, which may be termed «the golden age of antibiotics». Over the past three decades, the development of new antibiotics has largely stalled, while antibiotic resistance has increased. This situation may require new strategies for the treatment of infectious diseases.
a)17世纪在南美洲发现了金鸡纳树树皮和吐根灌木丛干燥根中的生物碱提取物,事实证明它们分别对疟疾(奎宁)和阿米巴痢疾(依米丁)有效;b)合成药物的发展,这主要发生在德国,始于保罗·埃尔利希(1854 - 1915)发现胂凡纳明(1909年),并以格哈德·多马克(1895 - 1964)发现磺胺类药物(20世纪30年代)达到顶峰;c)抗生素的发现。后者的主要例子是20世纪20年代末青霉素的研发,这是由一位从未在团队中工作、也从未作为研究项目一部分的独立研究科学家发现的。又过了大约十年才生产出药物级青霉素,此时的研究依赖于大型合作团队进行,这些团队通常由大学和富有的工业公司组成。对新抗生素的探索在20世纪40年代后半期认真开始,并且主要基于土壤微生物。在这一时期发现了许多新抗生素,这一时期可被称为“抗生素黄金时代”。在过去三十年里,新抗生素的研发基本停滞,而抗生素耐药性却有所增加。这种情况可能需要治疗传染病的新策略。