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医学里程碑—过去的五百年(编译)
作者:USMedEdu
发表时间:2008-02-13
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医学里程碑—过去的五百年
http://www.dxy.cn/bbs/post/view?bid=116&id=11096058&sty=1&tpg=1&age=0

编译:520香烟



新英格兰医学杂志(New Engl J Med 342: 42-49, 2000)在千年要结束的时候评论了过去的千年里最重要的医学发展。他们选择这些“发展”,限定的范围是“改变了临床医学的面貌,而非预防医学或者公共卫生或者分娩保健或者医学伦理学”。他们人意的选择了11项,将它们以“不是按照重要性排序,而是粗略的以在给定的领域迈出显著一步的年代顺序”予以公布。

文艺复兴之前临床医学方面几乎没有什么进步,“没什么进步的原因有很多”“其中肯定有一个原因是在那几个世纪学者追求的只是对神的认知,而非人。直到以人文主义特征的文艺复兴开始才有了改变…”所以,过去千年里比较主要的发展其实主要是在过去的500年里。下面就是NEJM以题纲形式公布的主要发展.

人体解剖学和生理学的阐明

当代解剖学值得注目的第一步:16世纪
创始人物:Andreas Vesalius在1543年公开发表了他非常重要的解剖学论述。配有的图示(一个不知名的画家画的)为理解人体解剖提供了一个新的标准。

生理学值得注目的第一步:17世纪
创始人物:William Harvey确定了血液循环是一个封闭的系统,心脏起到了泵的作用;脉搏是由心脏收缩后动脉被血液充盈产生;心脏右心室把血液泵到两肺;、左心室把血液泵到身体的其他部分。
其他的重要人物:Stephen Hales(第一次测量血压[在马身上]);Werner Forssmann, Andre Cournand, 和 Dickinson Richards(临床应用心导管插入术);还有Robert Gross, Elliott Cutler, Charles Hufnagel, 和 Alfred Blalock(心脏直视手术)

细胞和它们的基础结构的发现

细胞生物学值得注目的第一步:17世纪
创始人物:Antony van Leeuwenhoek,把物体接近他做的透镜(他近视)第一次能看到了微小的“微动物”(很可能是细菌和原虫),从而发现了组织包括了复杂的内部结构。
其他的重要人物:Robert Hooke(描述了植物细胞);Matthias Schleiden 和 Theodor Schwann(描述了动物细胞);还有Rudolf Virchow, Ludwig Aschoff, 和 Carl Rokitansky(他们在细胞生物学方面的工作引导了对疾病过程的洞察)

亚细胞生物学值得注目的第一步:20世纪
创始人物:Ernst Ruska在20世纪30年代初期制作了第一个电子显微镜。从最初的原始装置到后来的更高级的机器,细胞丰富的亚细胞结构变得可见了。
其他的创始人物:George Palade在20世纪50年代发展了分离亚细胞成分(例如线粒体)的方法。“各种细胞类型的不同成分的巧妙舞蹈最终可以被鉴定出来”

生命化学的阐明

生物化学值得注目的第一步:17世纪
创始人物:Thomas Willis在1659年开始有了“每种疾病的悲剧发生都是由一些酵素的力量造成的”这一主张被一些科学家夸大,例如Antoine Lavoisier, Jons Jakob Berzelius,和Louis Pasteur.
其他重要人物:Amadeo Avogadro(他提出的法则可以计算原子量,分子结构的测定和对酶反应的理解); Leonor Michaelis 和 Maud Menten(发现如何用数学术语表达酶反应);Otto Warburg(演绎出新陈代谢的路径);还有Hans Krebs(发现了称为三羧酸循环的路径)。
其他重大发现:荷尔蒙和神经递质;细胞之间的信息传导路径(帮助理解认识疾病,像糖尿病);钠与水中和脱水的关系;钾在腹泻液体丢失中的重要性。

统计学在医学上的应用

现代统计学值得注目的第一步:17世纪交替时期
创始人物:Pierre de Fermat and Blaise Pascal发展了概率论,用其分析偶然事件。17世纪的伦敦,他们相对频数的想法被第一次应用在瘟疫的死亡率上面。
著名的临床试验:James Lind治疗12个船上的败血症乘客,给他们含有柑橘汁的配剂或者船上的医生推荐的药物治疗剂。含有柑橘汁的配剂组的成功导致英国海军上将指令所有的水手(成为英国海军的人)储备酸橙汁,从而除去皇家海军中的败血症。
其他统计学上的重要人物:John Graunt(从一项潜在的人口数和描述预期寿命的样本中引进了推论的概念);Karl Friedrich Gauss(发展了现代的统计推理);18世纪英国神学者Thomas Bayes(示范了如何将概率应用到归纳推论中);Sir Ronald Fisher(随机化原则,一种避免研究中的偏移的方法);还有Jerzy Neyman(估算和测试的理论)

现代流行病学值得注目的第一步:19世纪
创始人物:John Snow通过分析英国使用Broad大街泵水的人群中的疾病发生率证明了霍乱的传播是来自污染水。他在1854年通过移去污染水井的汲水手柄阻止了疾病的传播。
其他的重要人物:Richard Doll([在英国医师中]做了吸烟问题先驱性研究)

麻醉的发展

现代麻醉值得注目的第一步:19世纪
创始人物:在1799年,Humphry Davy在他牙疼时候吸入了一氧化二氮,从而发现了一氧化二氮的麻醉(减轻痛苦)的特性。他称之为“笑气”。
其他的重要人物:牙医Horace Wells(在1844年第一次使用一氧化二氮麻醉患者);他先前的助手,William Morton在麻萨诸塞州综合医院示范了乙醚麻醉);James Young Simpson(在1847年在一个妇女生产中投入使用氯仿麻醉);还有Harold Griffith(在1942年开始在外科手术中常规引进使用肌松药)。

微生物(细菌)和疾病之间关系的发现

发现微生物和疾病之间关系值得注目的第一步:19世纪
创始人物:Louis Pasteur确定细菌学为一门科学。他证明“所有活的东西,包括微生物,来自其他的活的东西”;他用加热处理(巴斯德杀菌法)来破坏微生物,展示给绵羊接种减毒炭疽杆菌从而保护它们避免得病, 发现狂犬病试剂,一种病毒,可以是减弱的;他的免疫接种可以使被疯狗咬过的年轻男孩避免以前致命的结果。
其他的重要人物:Robert Koch(纯培养分离出细菌的第一人,发现霍乱试剂和结核病的原因,使用他自己的标准[柯赫氏法则]来区别致病菌的非致病{良性}菌);还有Joseph Lister(使用石炭酸喷雾剂杀菌,坚持用消毒剂消毒手,器械和敷料,使其在大外科手术中更为安全)。

遗传和遗传学的阐明

遗传学值得注目的第一步:19世纪
创始人物:Gregor Mendel做试验,在1865年报道了他在豌豆性状分离上的结论。(Mendel的工作一直被忽略了,直到1902年William Bateson和其他人再次发现这点)。
其他的重要人物:Archibald Garrod(发现先天性代谢缺陷是遗传的);Thomas Hunt Morgan(绘制了基因沿着同原染色体分布的地图);George Beadle, Edward Tatum, 和 Boris Ephrussi(认为基因的功能相当于酶);Thomas Avery, Colin MacLeod, 和 Maclyn McCarty(发现DNA是遗传物质);Erwin Chargaff(描述了DNA的主要成分和碱基配对法则);Rosalind Franklin(通过DNA的X线衍射图片揭示了双螺旋模型); James Watson, Francis Crick, 和 Maurice Wilkins(双螺旋模型);Jacques Monod 和 Francois Jacob(DNA通过信使RNA表达为蛋白质);Frederick Sanger 和 Walter Gilbert(创造了解码DNA碱基序列的方法);还有David Baltimore 和 Harold Temin(发现了逆转录酶,可以将RNA转变为DNA)〉
著名的序列研究:1949年在从丹佛开至芝加哥的火车上,William Castle告诉Linus Pauling镰状细胞性贫血。Pauling和同事证实了突变的分子结果(镰珠蛋白)导致遗传病(镰状细胞性贫血),将其命名为“分子病”(这种镰刀状变异不久之后被Vernon Ingram证实是由单一的分子单氨基酸置换导致)

免疫系统的认识

免疫学值得注目的第一步:19世纪
创始人物:Emil Behring 和 Kitasato Shibasaburo在1890年发现了白喉抗毒素,在这个过程中发现了抗体。几乎在同时,Elie Metchnikoff鉴定出吞噬细胞,这种细胞可以吞噬外来的颗粒,推动了免疫学的细胞理论。
其他的重要人物:John Enders(麻疹活疫苗); Thomas Weller, Frederick Robbins 和 Enders(脊髓灰质炎疫苗);Albert Sabin(减毒脊髓灰质炎病毒);Jonas Salk(灭活疫苗);还有Michael Heidelberger(为肺炎球菌疫苗奠定基础)
第一个疫苗是通过DNA生产的(为预防肝炎),在1986年被FDA认可。新千年里“建立在DNA序列上的疫苗很有可能发生革命性的变化,可能编译微生物抗原)

人体影像的发展

人体影像值得注目的第一步:20世纪交替时期
创始人物:Wilhelm Konrad Roentgen在1895年发现X线,因此他获得了1901年的第一届物理学诺贝尔奖。
第一阶段:影像学可以分为三个阶段。在第一阶段,目标是发展显像技术来解释内脏器官的解剖学特征和功能。为了达到这一目的,除了放射线,还有超声和放射线示踪器和造影剂在揭示先前看不见的结构的过程中发展起来。
第二阶段:通过血管造影术描述心脏和血管内部。其他的新工具,包括计算机体层摄影术(CT or CAT 扫描)和(核)磁共振影像学(MRI),有非常小的分辨率,可以看到人体各处非常小的结构。
第三阶段:成像方法现在被直接用于指导治疗。从长期的肿瘤治疗指导到近期的联机的最低限度的侵袭性手术。

抗微生物制剂的发现

抗微生物制剂发现值得注目的第一步:20世纪交替时期
创始人物:Paul Ehrlich发现了治疗梅毒的阿斯凡纳明(也被称做“606”,他尝试过606次),证实这种染料也有抗菌活性。
其他的重要人物:Gerhard Domagk(发现红色染料偶氮磺胺可以治愈链球菌属感染,发展成为磺胺类药物);Alexander Fleming(偶然发现霉菌,青霉菌,可以抑制葡萄球菌属细菌);Howard Florey 和 Ernst Chain(纯化了青霉素将其应用到临床);Rene Dubos(在土壤里一种生物体力发现了一种抗生素);还有Selman Waksman(系统研究土壤有机体和抗生素,发现了临床第二重要的抗生素,链霉素)

分子药物疗法的发展

分子药物疗法值得注目的第一步:20世纪交替时期
创始人物:在他做有机染料的治疗学潜能的实验过程中,Paul Ehrlich将之命名为“化学疗法”,扩展了从传染性疾病到癌症的“魔术弹”概念。
其他的重要人物:Thomas Beatson(乳腺癌患者做卵巢切除术[切去卵巢]);Charles Huggins(证实了睾丸切除术[切除睾丸]对前列腺癌的价值);Alfred Gilman 和 Frederick Philips(发现氮芥—第一次世界大战中的芥子气—帮助治疗淋巴瘤);Sidney Farber(引进甲氨喋呤治疗儿童时期的白血病); Barnett Rosenberg(发现抗癌药顺铂);还有 James Black(他的工作促进了β-阻滞剂的发展)。分子生物学的进行性革命提供了识别大量新的潜在药物靶点的可能,遗传药理学开始解释人们在对药物反应中的遗传变异性。

结论
有效的治疗和疾病的预防“和近几十年医师的最乐观的希望相比还是延长了预期寿命,减少了疾病,比一千年前他们的祖先的梦想的进步更大了。我们也像他们一样无法预言新千年将给我们带来些什么”。

Medical Milestones - The Past 500 Years

The New England Journal of Medicine (NEJM) commented on the end of the millennium by choosing the most important medical developments of the past thousand years. Their choices were restricted to developments that "changed the face of clinical medicine, not preventive medicine or public health or health care delivery or medical ethics." They arbitrarily chose 11 and presented them "not in order of importance, but in rough chronologic order according to the first noteworthy step taken in a given area."

There were few advances in clinical medicine until the Renaissance. "There are many reasons little progress was made" until then "but one of them was surely that the only fit pursuit for scholars in those centuries was considered to be knowledge of God, not of man. Only with the flowering of humanism that characterized the Renaissance did that change…." So, the major developments of the past millennium are really those of the past 500 years. Here are the major developments as presented by NEJM in outline form.

1. Elucidation of Human Anatomy and Physiology

First noteworthy step in contemporary anatomy: 16th century.

Founding figure: Andreas Vesalius in 1543 published his great anatomical treatise. The illustrations (by an unknown artist) set a new standard for the understanding of human anatomy.

First noteworthy step in physiology: 17th century.

Founding figure: William Harvey established that the blood circulates within a closed system with the heart serving as a pump; the pulse is due to the filling of arteries with blood after the heart contracts; the right ventricle of the heart pumps blood to the lungs; and the left ventricle pumps blood to the rest of the body.

Other major figures: Stephen Hales (first measured blood pressure [in a horse]); Werner Forssmann, Andre Cournand, and Dickinson Richards (the clinical use of heart catheterization); and Robert Gross, Elliott Cutler, Charles Hufnagel, and Alfred Blalock (open-heart surgery).

2. Discovery of Cells and Their Substructures


First noteworthy step in cell biology: 17th century.

Founding figure: Antony van Leeuwenhoek, with an object held close to the lens he had made (and with his nearsightedness) was first able to see minute "animalcules" (probably bacteria and protozoa) and discover that tissues had complex inner structures.

Other major figures: Robert Hooke (described plant cells); Matthias Schleiden and Theodor Schwann (described animal cells); and Rudolf Virchow, Ludwig Aschoff, and Carl Rokitansky (their work in cell biology led to insights into disease processes).

First noteworthy step in subcellular biology: 20th century.

Founding figure: Ernst Ruska made the first electron microscope in the early 1930s. With this primitive apparatus and, later, more sophisticated machines, the rich subcellular structure of the cell became visible.

Another founding figure: George Palade in the 1950s developed ways of isolating subcellular elements such as mitochondria. "The elegant choreography of the various elements in particular cell types could finally be appreciated."

3. Elucidation of the Chemistry of Life


First noteworthy step in biochemistry: 17th century.

Founding figures: Thomas Willis set forth the idea in 1659 that "every Disease acts its tragedies by the strength of some Ferment." This notion was amplified by scientists such as Antoine Lavoisier, Jons Jakob Berzelius, and Louis Pasteur.

Other major figures: Amadeo Avogadro (whose law permitted the calculation of atomic weights, the determination of molecular structure and an understanding of the enzyme reactions); Leonor Michaelis and Maud Menten (who found how to express enzyme reactions in mathematical terms); Otto Warburg (who deduced pathways of metabolism); and Hans Krebs (who discovered the pathway called the citric acid cycle).

Other major discoveries: Hormones and neurotransmitters; the ways cells communicate with each other (which has led to an understanding of diseases such as diabetes mellitus); the relation of sodium to edema and to dehydration; and the importance of potassium in the fluid loss from diarrhea.

4. Application of Statistics to Medicine


First noteworthy step in modern statistics: Turn of the 17th century.

Founding figures: Pierre de Fermat and Blaise Pascal developed probability theory to analyze games of chance. Their ideas of relative frequency were first applied to mortality from the plague in 17th-century London.

Famous clinical trial: James Lind treated 12 ship passengers who had scurvy with either an elixir containing citrus juice or a remedy recommended by the ship's surgeon. The success of the citrus-containing treatment led the British Admiralty to mandate the provision of lime juice to all sailors (who became limeys), thereby eliminating scurvy from the Royal Navy.

Other major figures in statistics: John Graunt (introduced the concept of inference from a sample to an underlying population and described life expectancy); Karl Friedrich Gauss (developed modern statistical reasoning); the 18th-century English theologian Thomas Bayes (showed how probability can be used in inductive reasoning); Sir Ronald Fisher (the principle of randomization as a method for avoiding bias in studies); and Jerzy Neyman (the theories of estimation and testing).

First noteworthy step in modern epidemiology: 19th century.

Founding figure: John Snow demonstrated the transmission of cholera from contaminated water by analyzing disease rates among people served by the Broad Street Pump in London. He stopped the spread of the disease in 1854 by removing the pump handle from the polluted well.

Another major figure: Richard Doll (who did a pioneering study of smoking [among British physicians!]).

5. Development of Anesthesia


First noteworthy step in modern anesthesia: 19th century.

Founding figure: In 1799 Humphry Davy recognized the analgesic (pain-relieving) properties of nitrous oxide when he inhaled it while he had a toothache. He coined the term "laughing gas."

Other major figures: The dentist Horace Wells (who in 1844 first used nitrous oxide to anesthetize patients); his former partner, William Morton (who demonstrated ether anesthesia in 1846 at the Massachusetts General Hospital); James Young Simpson (who in 1847 administered chloroform to a woman in childbirth): and Harold Griffith (who introduced the routine use of muscle relaxants during surgery in 1942).

6. Discovery of the Relation of Microbes to Disease


First noteworthy step in discovering the relation of microbes to disease: 19th century.

Founding figure: Louis Pasteur established bacteriology as a science. He proved that "all living things, microbes included, come from other living things"; he used heat treatment (pasteurization) to destroy microbes, showed that vaccination of sheep with weakened anthrax bacteria protects them against the disease, and discovered that the agent of rabies, a virus, could be weakened; his immunization of a young boy bitten by a rabid dog prevented what had been a fatal outcome.

Other major figures: Robert Koch (first person to isolate bacteria in pure culture; discovered the agents of cholera and the cause of tuberculosis, and used his own criteria [Koch's postulates] to distinguish a bacterial culprit causing a disease from an innocent microbe); and Joseph Lister (who used carbolic acid spray to kill bacteria, insisted that antiseptics be used on hands, instruments, and dressings and made it safe to do major surgery).

7. Elucidation of Inheritance and Genetics


First noteworthy step in genetics: 19th century.

Founding figure: Gregor Mendel did experiments and reported his results on the segregation of traits in peas in 1865. (Mendel's work was ignored until 1902, when William Bateson and others rediscovered it.)

Other major figures: Archibald Garrod (who showed that inborn errors of metabolism are inherited); Thomas Hunt Morgan (who drew maps of genes along chromosomes); George Beadle, Edward Tatum, and Boris Ephrussi (who showed that genes specify enzymes); Thomas Avery, Colin MacLeod, and Maclyn McCarty (who found that DNA is the genetic material); Erwin Chargaff (who described the bases of DNA and the rules of base pairing); Rosalind Franklin (whose x-ray diffraction pictures of DNA permitted the discovery of the double helix); James Watson, Francis Crick, and Maurice Wilkins (the double helix); Jacques Monod and Francois Jacob (DNA to protein via messenger RNA); Frederick Sanger and Walter Gilbert (who created methods for decoding the sequence of bases in DNA); and David Baltimore and Harold Temin (who discovered reverse transcriptase, which converts RNA into DNA).

Famous train ride: On a train from Denver to Chicago in 1949, William Castle told Linus Pauling about sickle cell anemia. Pauling and coworkers then demonstrated the molecular consequence of a mutation (sickle hemoglobin) that causes a genetic disorder (sickle cell anemia) and termed it "a molecular disease." (The sickle mutation was later shown by Vernon Ingram to be due to a single amino acid substitution in the molecule).

8. Knowledge of the Immune System


First noteworthy step in immunology: 19th century.

Founding figures: Emil Behring and Kitasato Shibasaburo in 1890 developed a diphtheria antitoxin and, in the process, discovered antibodies. Almost simultaneously, Elie Metchnikoff identified cells called phagocytes that can engulf foreign particles and put forth the cellular theory of immunity.

Other major figures: John Enders (measles vaccine) ; Thomas Weller, Frederick Robbins and Enders (the polio vaccine); Albert Sabin (the live weakened polio virus); Jonas Salk (the killed-virus vaccine); and Michael Heidelberger (laid the foundation for the pneumococcal vaccines).

The first vaccine produced by DNA technology (for hepatitis B) was approved by the Food and Drug Administration in 1986. The new millennium "promises a potentially revolutionary form of vaccination based on sequences of DNA that encode microbial antigens."

9. Development of Body Imaging


First noteworthy step in body imaging: Turn of the 20th century.

Founding figure: Wilhelm Konrad Roentgen discovered x-rays in 1895, a discovery for which he received the first Nobel prize for physics in 1901.

First stage: Imaging science has evolved in three stages. In the first stage, the aim was to develop imaging techniques to define the anatomic features and functions of the internal organs. Additional "rays" for this purpose were discovered, including ultrasound and radioactive tracers, and contrast agents were developed to reveal previously indiscernible structures.

Second stage: The interior of the heart and blood vessels were delineated by angiography. Other new tools included computed tomography (CT or CAT scan) and magnetic resonance imaging (MRI), which permitted resolution of very small structures throughout the body.

Third stage: Imaging methods are now being used to guide therapy directly -- from long-term guidance of cancer therapy to immediate, on-line guidance of minimally invasive surgery.

10. Discovery of Antimicrobial Agents


First noteworthy step in the discovery of antimicrobial agents: Turn of the 20th century.

Founding figure: Paul Ehrlich discovered salvarsan (also known as "606," the 606th compound he had tried) as a treatment for syphilis and showed that certain dyes also had antimicrobial activity.

Other major figures: Gerhard Domagk (who found that the red dye Prontosil cured strep infections, which led to the development of the sulfa drugs); Alexander Fleming (who stumbled onto the inhibition of Staph bacteria by a mold, Penicillium) ; Howard Florey and Ernst Chain (who purified penicillin for clinical use); Rene Dubos (who found an antibiotic in an organism in the soil); and Selman Waksman (who searched systematically among soil organisms for antibiotics and there discovered the second clinically important antibiotic, streptomycin).

11. Development of Molecular Pharmacotherapy


First noteworthy step in molecular pharmacotherapy: Turn of the 20th century.

Founding figure: In the course of his experiments on the therapeutic potential of organic dyes, Paul Ehrlich coined the word "chemotherapy" and extended the concept of the "magic bullet" from infectious diseases to cancer.

Other major figures Thomas Beatson (who used ovariectomy [removal of the ovaries] for breast cancer); Charles Huggins (showed value of orchiectomy [removal of the testes] for prostate cancer). Alfred Gilman and Frederick Philips (found that nitrogen mustard -- the mustard gas of World War I - helped treat lymphomas); Sidney Farber (introduced methotrexate for treating childhood leukemia); Barnett Rosenberg (discovered the anticancer drug cis- platinum); and James Black (whose work led to the development of beta- blockers).

The ongoing revolution in molecular biology permits the recognition of a great number of new potential drug targets, while pharmacogenetics is beginning to explain the genetic variability among people in their responses to drugs.


Conclusions

The effective treatment and prevention of disease has "extended life expectancy and reduced disability beyond the most optimistic hopes of physicians even a few decades ago -- and far beyond the dreams of their predecessors a thousand years ago. We are no more able than they were to predict what this new millennium will bring."
SourceThe Editors. Looking back on the millennium in medicine. New Engl J Med 342: 42-49, 2000.

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