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2021-02-24 16:11
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Introduction to Physiology



Introduction



Physiology


is


the


study


of


the


functions


of


living


matter.


It


is


concerned


with


how


an


organism


performs


its


varied


activities:


how


it


feeds,


how


it


moves,


how


it


adapts


to


changing


circumstances,


how


it


spawns new generations. The subject is vast and embraces the whole of


life. The success of physiology in explaining how organisms perform their


daily


tasks


is


based


on


the


notion


that


they


are


intricate


and


exquisite


生理学简介



介绍



生理学是研究生物体功能的科学 。它


研究生物体如何进行各种活动,如何饮食,


如何运动,


如何适应不断改变的环境,


如何


繁殖后代。


这门学科包罗万象,


涵盖了生物


体整个 生命过程。生理学成功地解释了生


物体如何进行日常活动,基于的观点是生


machines


whose


operation


is


governed


by


the


laws


of


physics


and


chemistry.



Although some processes are similar across the whole spectrum of


biology—the replication of the genetic code for or example—many are


specific to particular groups of organisms. For this reason it is necessary


to divide the subject into various parts such as bacterial physiology, plant


physiology, and animal physiology.



To study how an animal works it is first necessary to know how it is


built. A full appreciation of the physiology of an organism must therefore


be based on a sound knowledge of its anatomy. Experiments can then be


carried


out


to


establish


how


particular


parts


perform


their


functions.


Although there have been many important physiological investigations on


human


volunteers,


the


need


for


precise


control


over


the


experimental


conditions has meant that much of our present physiological knowledge


has been derived from studies on other animals such as frogs, rabbits, cats,


and


dogs.


When


it


is


clear


that


a


specific


physiological


process


has


a


common


basis


in


a


wide


variety


of


animal


species,


it


is


reasonable


to


assume


that


the


same


principles


will


apply


to


humans. The


knowledge


gained


from


this


approach


has


given


us


a


great


insight


into


human


physiology


and


endowed


us


with


a


solid


foundation


for


the


effective


treatment of many diseases.



The


building


blocks


of


the


body


are


the


cells,


which


are


grouped


together


to


form


tissues.


The


principal


types


of


tissue


are


epithelial,


connective,


nervous,


and


muscular,


each


with


its


own


characteristics.


Many connective tissues have relatively few cells but have an extensive


extracellular


matrix.


In


contrast,


smooth


muscle


consists


of


densely


packed layers of muscle cells linked together via specific cell junctions.


Organs such as the brain, the heart, the lungs, the intestines, and the liver


are formed by the aggregation of different kinds of tissues. The organs are


themselves parts of distinct physiological systems. The heart and blood


vessels form the cardiovascular system; the lungs, trachea, and bronchi


together with the chest wall and diaphragm form the respiratory system;


the skeleton and skeletal muscles form the musculoskeletal system; the


brain, spinal cord, autonomic nerves and ganglia, and peripheral somatic


nerves form the nervous system, and so on.



Cells


differ


widely


in


form


and


function


but


they


all


have


certain


common


characteristics.


Firstly,


they


are


bounded


by


a


limiting


membrane, the plasma membrane. Secondly, they have the ability to break

物体好比是结构复杂而灵巧的机器,其操


作受物理和化学规律控制。



尽管从生物学整个范畴看,生物体某


些活动过程是相 似的


——


如基因编码的复


< p>
——


但许多过程还是某些生物体群组特


有的。鉴于 此有必要将这门学科分成不同


部分研究,


如细菌生理学、


植物生理学和动


物生理学。



要研究一种动物如何活动,首先需要


了解它的构成。要充分了解一个生物体的< /p>


生理学活动就必须掌握全面的解剖学知


识。一个生物体的各部分起 着什么作用可


通过实验观察得知。尽管我们对志愿者进


行了许多 重要的生理调查,但是实验条件


需要精确控制,所以我们当前大多生理知


识还是源于对其它动物如青蛙,


兔子,


猫和

< p>
狗等的研究。当我们明确大多数动物物种


的特定生理过程存在共同之处时, 相同的


生理原理适用于人类也是合理的。通过这


种方法,


我们获得了大量的知识,


从而让我


们对人类生 理学有了更深入的了解,为我


们有效治疗许多疾病提供了一个坚实的基

< br>础。



机体的基本组成物质是细胞,细胞结


合在一起形成组织。组织的基本类型有上


皮组织,


结 缔组织,


神经组织和肌组织,



类组织 都有各自的特征。许多结缔组织中


细胞量相对较少,但是有大量的细胞外基


质。


相比而言,


光滑的肌组织由大量密密麻


麻的肌细胞通过特定的细胞连接组成。各


种器官如脑,

< br>心脏,


肺,


小肠和肝等由不同


种 类的组织聚集而成。这些器官是不同生


理系统的组成部分。心脏和血管组成心血


管系统;


肺,


器官,


支 气管,


胸壁和膈肌组


成呼吸系统;骨骼和骨骼肌组成骨骼肌系< /p>


统;


大脑,


脊髓,


自主神经和神经中枢以及


周围躯体神经组成神经系统等等。



细胞在形体和功能上差异很大,但是



down large molecules to smaller ones to liberate energy for their activities.


Thirdly, at some point in their life history, they possess a nucleus which


contains genetic information in the form of deoxyribonucleic acid (DNA).



Living


cells


continually


transform


materials.


They


break


down


glucose and fats to provide energy for other activities such as motility and


the synthesis of proteins for growth and repair. These chemical changes


are collectively called metabolism. The breakdown of large molecules to


smaller


ones


is


called


catabolism


and


the


synthesis


of


large


molecules


from smaller ones anabolism.



In


the


course


of


evolution,


cells


began


to


differentiate


to


serve


它们有某些共同的特征。


第一,


它们由限制


膜包被,


即细胞质膜 ;


第二,


细胞有把大分


子分解为小分子 来释放活动所需能量的能


力;


第三,


在 生命过程中某个阶段,


细胞体


内存在一个以脱氧核糖核酸


(DNA)


形式包


含基因信息的细胞核。



活体细胞不断转化物质。它们为其它


活动 提供能量分解葡萄糖和脂肪,比如自


身生长和修复所需的蛋白质运动和合成。

< p>
这些化学变化统称为新陈代谢。把大分子


different functions. Some developed the ability to contract (muscle cells),


others


to


conduct


electrical


signals


(nerve


cells).


A


further


group


developed the ability to secrete different substances such as hormones or


enzymes.


During


embryological


development,


this


process


of


differentiation


is


re-enacted


as


many


different


types


of


cell


are


formed


from the fertilized egg.



Most


tissues


contain


a


mixture


of


cell


types.


For


example,


blood


consists of red cells, white cells, and platelets. Red cells transport oxygen


around the body. The white cells play an important role in defense against


infection and the platelets are vital components in the process of blood


clotting. There are a number of different types of connective tissue but all


are


characterized


by


having


cells


distributed


within


an


extensive


noncellular matrix. Nerve tissue contains nerve cells and glial cells.



The Principal Organ Systems



The cardiovascular system


The cells of large multicellular animals cannot derive the oxygen and


nutrients they need directly from the external environment. The oxygen


and nutrients must be transported to the cells. This is one of the principal


functions of the blood, which circulates within blood vessels by virtue of


the pumping action of the heart. The heart, blood vessels, and associated


tissues form the cardiovascular system.



The heart consists of four chambers, two atria and two ventricles,


which


form


a


pair


of


pumps


arranged


side


by


side. The


right


ventricle


pumps deoxygenated blood to the lungs where it absorbs oxygen from the


air, while the left ventricle pumps oxygenated blood returning from the


lungs to the rest of body to supply the tissues. Physiologists are concerned


with establishing the factors responsible for the heartbeat, how the heart


pumps the blood around the circulation, and how it is distributed to perfuse


the tissues according to their needs. Fluid exchanged between the blood


plasma and the tissues passes into the lymphatic system, which eventually


drains back into the blood.



The respiratory system


The energy required for performing the various activities of the body


is ultimately derived from respiration. This process involves the oxidation


of foodstuffs to release the energy they contain. The oxygen needed for


分解为小分子的过程称为分解代谢,小分


子合成大分子的过程称为合成 代谢。



细胞在进化过程中不断分化进行不同

< br>的功能活动。


有些细胞具有收缩能力


(如肌


细胞)


,有些可以传导电信号(如神经细


胞)


。进一步进化的细胞能够分泌不同物质


如荷尔蒙


(如内分泌细胞)


或酶。


胚胎发育


过 程中,分化的过程由于很多不同细胞来


源于受精卵而再次发生。



大多数组织包含有不同的细胞类型。


比如,血液中含红细胞,白 细胞和血小板。


红细胞运输全身的氧气。白细胞在抵御感


染时起 重要作用,血小板是血液凝集过程


中重要的成分。结缔组织有多种不同类型,

< p>
但有一个共同特征,即细胞分布在丰富的


细胞外基质中。神经组织含神经细 胞和神


经胶质细胞。



主要的器官系统



心血管系统



大型多细胞动物体的细胞 不能从外界


环境中获取直接所需的氧气和营养物质。


这些氧气和 营养物质必须转运到细胞。这


是血液的主要功能之一,血液凭借心脏的

< br>泵血作用在血管内流动循环。


心脏、


血管和


结缔组织组成了心血管系统。



心脏包括四个腔,两 个心房和两个心


室构成了一对并排存在的泵。右心室将脱


氧的血 液泵至肺中,肺中的血液吸收空气


中的氧气,而左心室把从肺回流来的有氧


血液泵出至身体其它部位,供应给各组织。


生理学家研究促使心脏跳动的因素 ,心脏


如何泵送血液使其循环,心脏如何根据各


组织所需分配血 液。血浆和组织间的流动


液体交换流入淋巴系统,最终回流到血液


中。




this process is absorbed from the air in the lungs and carried to the tissues


by the blood. The carbon dioxide produced by the respiratory activity of


the tissues is carried to the lungs by the blood in the pulmonary artery


where it is excreted in the expired air. The basic questions to be answered


include the following: How is the air moved in and out of the lungs? How


is


the


volume


of


air


breathed


adjusted


to


meet


the


requirements


of


the


body? What limits the rate of oxygen uptake in the lungs?



呼吸系统



机体进行各项活动所需的能 量最终来


源于呼吸。


这一过程包括食物


(主要是糖类


和脂肪)


的氧化,


释放它 们所含的能量。



一过程中,


氧气来自 于肺中的空气,


经由血


液到达全身各组织。组织呼吸活动中释放


的二氧化碳由肺动脉中的血液运送至肺,


The digestive system


然后呼气排出体外。需回答的基本问题如


The nutrients needed by the body are derived from the diet. Food is


下:空气是如何进出肺的?呼吸的空气量


taken


in


by


the


mouth


and


broken


down


into


its


component


parts


by


如何适应机体所需?限制肺吸收氧气频率


enzymes


in


the


gastrointestinal


tract.


The


digestive


products


are


then


的因素是什么?



absorbed into the blood across the wall of the intestine and pass to the liver


消化系统



via the portal vein. The liver makes nutrients available to the tissues both


for their growth and repair and for the production of energy. In the case of


机体所需营养物质来源于饮食。食物


the


digestive


system,


key


physiological


questions


are:


How


is


food


经口腔进入体内,在胃肠道内经酶将其分


ingested? How is it broken down and digested? How are the individual


解成小分子物质。这些消化物通过肠壁吸


nutrients absorbed? How is the food moved through the gut? How are the


收入血液,


通过门静脉进入肝脏。< /p>


经肝脏作


indigestible remains eliminated from the body?



用后 ,这些营养物质能够满足组织生长修


复及能量需求。


在消化系统 部分,


重要的生


The kidneys and urinary tract


理学问题是:食物是如何消化的?食物如


The chief function of the kidneys is to control the composition of the


何被个体分解消化?个体营养物质如何吸


extracellular fluid. In the course of this process, they also eliminate non-


收 ?食物如何在肠内转运的?未消化的残


volatile waste products from the blood. To perform these functions, the


留如何从体内排出?



kidneys produce urine of variable composition which is temporarily stored


泌尿系统



in the bladder before voiding. The key physiological questions in this case


are: how do the kidneys regulate the composition of the blood? How do


肾脏主要功能是控制细胞外液体的形


they


eliminate


toxic


waste?


How


do


they


respond


to


stresses


such


as


成。


在这一过程中,


肾脏也会把不可挥 发的


dehydration? What mechanisms allow the storage and elimination of the


废物排出去。为行使这一功能,在排出之


urine?



前,肾脏产生含有各种成分的尿液并将其

暂时储存在膀胱中。这一部分主要的生理


The reproductive system


学问题是:肾脏如何调节血液中的成分?


Rep roduction


is


one


of


the


fundamental


characteristics


of


living


如何排出有毒废物?如何应对像脱水这样


organisms. The gonads produce specialized sex cells known as gametes.


的应激反应?以及尿液可以存储和排出体


At the core of sexual reproduction is the creation and fusion of the male


外的机制是什么?



and female gametes, the sperm and ova


(eggs), with the result that the


生殖系统



genetic characteristics of two separate individuals are mixed to produce


offspring that differ genetically from their parents.



生殖是活生物体的一个基本特征。生


殖腺产生专门的性细胞,

< br>被称为配子。


性生


The musculoskeletal system


殖的核心是雌雄配子即精子和卵子的产生


This consists of the bones of the skeleton, skeletal muscles, joints,


和融合,因此两个独立个体的基因特征融


and their associated tissues. Its primary function is to provide a means of


合而产生一个基因上与双亲不同的后代。




movement,


which


is


required


for


locomotion,


for


the


maintenance


of


运动系统



posture, and for breathing. It also provides physical support for the internal


organs. Here the mechanism of muscle contraction is a central issue. The


这一系 统由骨、


骨骼肌、


关节和它们的


end ocrine and nervous systems.



相关组织组成。其主要功能是提供运动需


要,


维持姿势及呼吸运 动。


它也为内脏器官


The endocrine and nervous systems


提供物理支持。


这一部分,


肌肉收缩机制是



The activities of the different organ systems need to be coordinated


and regulated so that they act together to meet the needs of the body. Two


coordinating systems have evolved: the nervous system and the endocrine


system. The nervous system uses electrical signals to transmit information


very rapidly to specific cells. Thus the nerves pass electrical signals to the


skeletal


muscles


to


control


their


contraction.


The


endocrine


system


secretes chemical agents, hormones, which travel in the bloodstream to


the cells upon which they exert a regulatory effect. Hormones play a major


role


in


the


regulation


of


many


different


organs


and


are


particularly


important


in


the


regulation of


the


menstrual


cycle


and other


aspects


of


reproduction.



The immune system provides the body’s defenses against infection


both


by


killing


invading


organisms


and


by


eliminating


diseased


or


damaged cells.



Although it is helpful to study how each organ performs its functions,


it


is


essential


to


recognize


that


the


activity


of


the


body


as


a


whole


is


dependent on the intricate interactions between the various organ systems.


If


one


part


fails,


the


consequences


are


found


in


other


organ


systems


throughout the whole body. For example, if the kidneys begin to fail, the


regulation of the internal environment is impaired which in turn leads to


disorders of function elsewhere.



主要问题。



内分泌系统和神经系统



不同器官系统 的活动需要协作和调


节,


以便共同作用满足机体需要。


人体有两


大调节系统:


神经系统和内分泌系统。


神经


系统通过电信号迅速将信息传导给特定细

< br>胞。这样神经将电信号传递给骨骼肌以控


制收缩。内分泌系统分泌化学物质



激素。


激素通过血流到达施与调节作用的细 胞。


激素在许多不同器官中起着重要作用,在


月经期调节和其它 生殖方面尤其重要。



免疫系统通过杀死入侵的有机体,清


除致病或损伤细胞为机体提供防御功能。



虽然研究各器官如何行使功能很有益


处,但我们必须认识到机体作为一个整体

< p>
所做的活动依赖于各器官系统间错综复杂


的相互作用。

如果一部分无法正常工作,



身其它器官系统也会受到影响 。


例如,


如果


肾脏出现问题,


内部环境的调节受损,


结果


导致其它器官系统功 能紊乱。



Homeostasis



Complex mechanisms are at work to regulate the composition of the


extracellular


fluid


and


individual


cells


have


their


own


mechanisms


for


regulating


their


internal


composition.


The


regulatory


mechanisms


stabilize the internal environment despite variations in both the external


world and the activity of the animal. The process of stabilization of the


internal environment is called homeostasis and is essential if the cells of


the body are to function normally.



Taking


one


example,


the


beating


of


the


heart


depends


on


the


rhythmical contractions of cardiac muscle cells. This activity depends on


electrical signals which, in turn, depend on the concentration of sodium


and potassium ions in the extracellular and intracellular fluids. If there is


an excess of potassium in the extracellular fluid, the cardiac muscle cells


become too excitable and may contract at inappropriate times rather than


in a coordinated manner. Consequently, the concentration of potassium in


the extracellular fluid must be kept within a narrow range if the heart is to


beat normally.



稳态



各种复杂机制共同作用调节细胞外液


的形成,不同个体细胞有自身机制调 节内


在组成成分。尽管外界环境和动物活动不


停变化,调节机制 维持着体内环境的稳定。


内部环境的稳定被称为稳态,它是机体能


够正常发挥作用所必须的。



例如,心脏的跳动依赖于心肌细 胞有


节律的收缩。


这一活动依赖于电信号,

而电


信号反过来依赖存在于细胞外和细胞内液


体中钠和钾离 子的浓度。如果细胞外液中


钾离子过多,


心肌细胞兴奋性增强,


可能出


现不规律的收缩。


因此,


要维持心脏正常跳


动,细胞外液中钾离子的浓度就必须控制

< p>
在一定范围内。



机体如何调节物质成分



平衡的概念



一天中,一个成人需要消 耗约


1


千克


食物,

2~3


升液体。


以一个月计算,


这 相当


于约


30


千克食物,


60~90


升液体。然而,


一般来说,


机体体重是基本不变的。


这类个


体可以说处于平衡状 态。食物和液体的摄


入量相当于正常机体活动消耗的能量加上


尿 液和粪便中丢失的能量。在一些情况下,


How Does The Body Regulate Its Own Composition?



The concept of balance


In the course of a day, an adult consumes approximately 1 kg of food


and drinks 2~3 liters of fluid. In a month, this is equivalent to around 30


kg of food and 60~90 liters of fluid. Yet, in general, body weight remains


remarkably constant. Such individuals are said to be in balance; the intake


of food and drink matches the amounts used to generate energy for normal



bodily activities plus the losses in urine and feces. In some circumstances,


such as starvation, intake does not match the needs of the body and muscle


tissue


is


broken


down


to


provide


glucose


for


the


generation


of


energy.


Here,


the


intake


of


protein


is


less


than


the


rate


of


breakdown


and


the


individual is said to have a negative nitrogen balance. Equally, if the body


tissues are being built up, as is the case for growing children, pregnant


women


and


athletes


in


the


early


stages


of


training,


the


daily


intake


of


protein is greater than the normal body turnover and the individual is in


positive nitrogen


balance.



This concept of balance can be applied to any of the body constituents


including


water


and


salt


and


is


important


in


considering


how


the


body


regulates its own composition. Intake must match requirements and any


excess must be excreted for balance to be maintained. Additionally, for


each chemical constituent of the body there is a desirable concentration


range,


which


the


control


mechanisms


are


adapted


to


maintain.


For


example, the concentration of glucose in the plasma is about 4~5mmol/L


between meals. Shortly after a meal, plasma glucose rises above this level


and this stimulates the secretion of the hormone insulin by the pancreas,


which


acts


to


bring


the


concentration


down.


As


the


concentration


of


glucose falls, so does the secretion of insulin. In each case, the changes in


the circulating level of insulin act to maintain the plasma glucose at an


appropriate level. This type of regulation is known as negative feedback.


During the period of insulin secretion, the glucose is being stored as either


glycogen or fat.



A negative feedback loop is a control system that acts to maintain the


level


of


some


variable


within


a


given


range


following


a


disturbance.


Although


the


example


given


above


refers


to


plasma


glucose,


the


basic


principle


can


be


applied


to


other


physiological


variables


such


as


body


temperature, blood pressure, and the osmolality of the plasma. A negative


feedback loop requires a sensor of some kind that responds to the variable


in question but not to other physiological variables. Thus an osmoreceptor


should


respond


to


changes


in


osmolality


of


the


body


fluids


but


not


to


changes in body temperature or blood pressure. the information from the


sensor must be compared in some way with the desired level by some form


of comparator. if the two do not match ,an error signal is transmitted to an


effector,


a


system


that


can


act


to


restore


the


variable


to


its


desired


level .these features of negative feedback can be appreciated by examining


a


simple


heating


system .the


controlled


variable


is


room


temperature,


which is sensed by a thermostat. the effector is a heater of some kind .when


the room temperature falls below the set point, the temperature difference


is detected by the thermostat which switches on the heater .this heats the


room until the temperature reaches the per set level whereupon the heater


is switched off.



To summarize, the body is actually a social order of about 100 trillion


cells


organized


into


different


functional


structures,


some


of


which


are


called organs. each functional structures its share to the maintenance of


homeostatic


conditions


in


the


extracellular


fluid,


which


is


called


the


internal long as normal conditions are maintained in this


如饥饿状态 ,摄入量与机体所需量并不相


当,


肌组织断裂,


提供葡萄糖产生能量。



白质的摄入低于肌组织断裂的 速度,机体


处于负氮平衡。


同样地,


如 果机体组织正处


于生长期,


如生长期的儿童,

< br>孕妇和早期训


练阶段的运动员,那么蛋白质的日常摄入


量 比正常机体所需要的多。


相反,


此时个体


处于


正氮


平衡。


< br>平衡的概念可以应用到机体的任何构


成成分上,


包括水和 盐,


而且平衡在机体调


节其自身成分上是非常重要的。摄入必须


等于所需,


为维持机体平衡,


任何多余 的能


量都必须排出。


此外,


因为机体的 每种化学


成分都有一个可取的浓度范围,控制机制


维持这个范围 。


例如,


两餐间血糖浓度大约



4~5mmol/L



进食后不久,


血糖含量超过


这一范围,刺激胰腺分泌胰岛素,降低浓

< br>度。


随着葡萄糖浓度的下降,


胰岛素分泌减


少。


在此情况下,


循环胰岛素水平的改变都


是为了使血浆中的葡萄糖维持在一个合适


的范围内。

这种调节称为负反馈机制。


在胰


岛素分泌期间,葡萄糖像肝 糖原或脂肪一


样被储存。



负反馈调节 是在机体出现紊乱时,将


一些变量控制在限定范围内的一个控制系


统。


虽然上面的例子讲到血糖,


但这一基本

< br>原则可以应用到其它生理变量中如体温、


血压和血浆的渗透浓度。负反馈调节需要


一种能对不确定的变量做出反应而对其它


生理变量不应答的传感 器。


因此,


渗透压感


受器应该能对机体 体液渗透的变化而不是


体温和血压的变化产生应答。感受器传递


的信息必须和理想水平


(系统的调定点)


比较者的身份,


以某种方式进行比较。


如果


两者不相符,一个错误信号就会传递给效


应器,效应器是一种能使变量保持在理 想


水平的系统。负反馈的这些特点可以通过


检测一种简单的加热 系统来理解。被控制


的变量是室温,它可以由一个温度计检测


到 ,


效应器是一种加热器。


当室温降低到调


定点以下时,温度计就可以监测到温度的


变化而开启加热器,


对室内进行加温,


直到


室温升高到先前调好的调定点,加热器关


闭。



总而言之,机体实际上是由


100


万亿


细胞有序组成了不同的功能结构 ,其中一


些被称为器官。每个功能结构都在维持细


胞外液稳态方 面发挥其作用,这称之为内



internal environment ,the cells of the body continue to live and function


properly.


Each


cell


benefits


from


homeostasis,


and


in


turn,


each


cell


contributes


its


share


toward


the


maintenance


of


homeostasis.


This


reciprocal


interplay


provides


continuous


automaticity


of


the


body


until


one or more functional systems lose their ability to contribute their share


of function. When this happens, all the cells of the body suffer. Extreme


dysfunction leads to death; moderate dysfunction leads to sickness.





环境。


只 要内部环境处于正常状态,


机体细


胞继续生存并正常运行。每个 细胞都从稳


态中获益,


反过来,


每个细 胞都为稳态做出


贡献。这种相互作用促使机体持续自主运


行,直 至一个或多个功能系统不能正常运


转。


此时,

< br>机体所有细胞都会受损。


功能极


度异常会导致死亡,轻微 的功能异常导致


疾病的发生。




The Other Side of Antibiotics



Antibiotics have eliminated or controlled so many infectious diseases


that virtually everyone has benefited from their



use at one time or another.


Even without such personal experience, however, one would have to be


isolated indeed to be



unaware of the virtues, real and speculative, of these


“miracle” drugs. The American press, radio, and television have



done a


good


job


of


reporting


the


truly


remarkable


story


of


successes


in


the


chemical war on germs. What’s more, any



shortcomings on their part have


been more than made up for by the aggressive public relations activity of


the pharmaceutical



companies which manufacture and sell antibiotics.



In


comparison,


the


inadequacies


and


potential


dangers


of


these


remarkable


drugs


are


much


less


widely


known. And


the


lack



of


such


knowledge


can


be


bad,


especially


if


it


leads


patients


to


pressure


their


doctors


into


prescribing


antibiotics


when



such


medication


isn’t


really


needed, or leads them to switch doctors until they find one who is, so to


speak,



antibiotics-minded.



Because the good side of the antibiotics story is so very well-known,


there seems more point here to a review of some of



the immediate and


long-range problems that can come from today’s casual use of these drugs.


It


should


be


made


clear


in



advance


that


calamities


from


the


use


of


antibiotics


are


rare


in


relation


to


the


enormous


amounts


of


the


drugs


administered. But the potential hazards, so little touched on generally, do


need


a


clear


statement.


The


antibiotics


are


not,


strictly



speaking,


exclusively prescription drugs. A number of them are permitted in such


over-the-counter products as nasal sprays,



lozenges, troches, creams, and


ointments. Even if these products do no harm, there is no point whatsoever


in


using


them.


If



you


have


an


infection


serious


enough


to


warrant


the


launching


of


chemical


warfare,


you


need


much


bigger


doses


of


the



antibiotics than any of the non-prescription products are allowed to


contain.



Over-the-counter


products,


however,


account


for


only


a


small


percentage of total antibiotics production. It is


the



prescription dosages


that


give


people


trouble.


These


drugs—even


allowing


for


the


diverse


abilities


of


the


many



narrow- spectrum


ones


and


the


versatility


of


the


broad- spectrum ones—are not the cure-alls, they often are billed as being.


There are wide gaps in their ability to master contagious diseases. Such


important infections as mumps, measles, common colds,



influenza, and


infectious


hepatitis


still


await


conquest.


All


are


virus


infections


and


despite intense efforts, very little



progress has been made in chemotherapy


against


viruses.


Only


small


progress


has


been


achieved


against


fungi.


Many strains of



bacteria and fungi are naturally resistant to all currently


available


antibiotics


and


other


chemotherapeutic


drugs.


Some



microorganisms


originally


sensitive


to


the


action


of


antibiotics,


especially staphylococcus, have developed resistant strains. This acquired


resistance imposes on the long range value of the drugs a very important


limitation,


which


is


not


adequately



met


by


the


frequent


introduction


of


new antimicrobial agents to combat the problem.



抗生素的另一面



抗生素已经消除或控制了很多传染


病,实际上每个人都从这种或 那种使用中


受益。


即使没有这样的个人经验,

< br>人们也不


得不孤立地认识到这些



奇迹



药物的优点,


真实性和推测性 。


美国新闻界,


广播电台和


电视台在报 道有关细菌化学战争成功的真


实故事方面做得很好。


更重要的是 ,


制造和


销售抗生素的制药公司的积极的公共关系


活动已经弥补了他们的缺点。



相比之下,这些显着 的药物的不足之


处和潜在的危险是广为人知的。缺乏这样


的知识 可能是不好的,特别是如果它导致


病人迫使他们的医生处方抗生素,当这种


药物是不是真的需要,或导致他们切换到


医生,


直到 他们找到一个谁可以说,


抗生素



-


头脑。



因为抗生素故事的好处是如此 众所周


知,在这里似乎更重要的是要回顾一下当


今随便使用这些 药物可能产生的一些近期


和远期问题。


应该预先说明,


使用抗生素造


成的灾难与所投入的大量药物有关。但是

< br>一般来说很少涉及的潜在危害确实需要一


个明确的说法。


严格来说,


抗生素不是完全


处方药。它们中的一些允许用于鼻腔 喷雾


剂,


锭剂,


锭剂,


霜剂和软膏等非处方产品。


即使这些产品没有坏处,使用它们也没有

< p>
任何意义。如果感染的严重程度足以保证


发动化学战争,则需要比任何非处 方产品


所含的抗生素剂量大得多的抗生素。


< br>然而,非处方药产品仅占抗生素总产


量的很小比例。这是给人们麻烦的处方剂


量。


这些药物,


即使考虑到许多窄谱药物的


多样性和广谱药物的多样性,也不是治愈


所有的药物,


他们往往被称为



药物




掌握


传染病的能力差距很大。像腮 腺炎,麻疹,


感冒,流行性感冒和传染性肝炎等重要感


染仍在等 待征服。所有这些都是病毒感染,


尽管付出了巨大的努力,但在化学疗法方


面进展甚微。


真菌只取得小的进展。


许多细


菌和真菌菌株对所有目前可用的抗生素和


其他化学治疗药物都具有天然的 抗性。一


些原本对抗生素作用敏感的微生物,特别


是葡萄球菌,


已经产生了耐药菌株。


这种获


得的耐药 性对药物的远距离价值提出了一


个非常重要的限制,而这种限制并不能通


过频繁引入新的抗菌剂来解决这个问题。




It


has


been


pretty


well


established


that


the


increase


in


strains


of


bacteria resistant to an antibiotic correlates



directly with the duration and


extent of use of that antibiotic in a given location. In one hospital a survey


showed that,



before erythromycin had been widely used there, all strains


of staphylococci taken from patients and personnel were



sensitive to its


action. When the hospital started extensive use of erythromycin, however,


resistant staphylococcus strains



began to appear.



The development of bacterial resistance can be minimized by a more


discriminating use of antibiotics, and the person



taking the drug can help


here.


When


an


antibiotic


must


be


used,


the


best


way


to


prevent


the


development


of


resistance


is


to



wipe


out


the


infection


as


rapidly


and


thoroughly as possible.


Ideally, this


requires a bactericidal drug, which


destroys,



rather than a bacteriostatic drug, which inhibits. And the drug


must be taken in adequate dosage for as long as it is



necessary to eradicate


the infection completely. The doctor, of course, must choose the drug, but


patients


can


help


by


being



sure


to


take


the


full


course


of


treatment


recommended by the doctor, even though symptoms seem to disappear


before all the



pills are gone. In rare instances the emergence of resistance


can be delayed or reduced by combinations of antibiotics. Treatment of


tuberculosis with streptomycin alone results in a high degree of resistance,


but if para-aminosalicylic acid or



isoniazid is used with streptomycin the


possibility that this complication will arise is greatly reduced.



In


hospital


treatment


of


severe


infections,


the


sensitivity


of


the


infecting


organism


to


appropriate


antibiotics


is



determined


in


the


laboratory before treatment is started. This enables the doctor to select the


most


effective


drug


or


drugs;



it


determines


whether


the


antibiotic


is


bactericidal


or


bacteriostatic


for


the


germs


at


hand; and


it


suggests


the


amount



needed to destroy the growth of the bacteria completely. In either


hospital or home, aseptic measures can help to reduce the



prevalence of


resistant strains of germs by preventing cross infection and the resultant


spreading of organisms.



Every one of the antibiotics is potentially dangerous for some people.


Several


serious


reactions


may


result


from


their



use.


One


is


a


severe,


sometimes fatal, shock-like anaphylactic action, which may strike people


who have become sensitized to



penicillin. Anaphylactic reaction happens


less frequently and is less severe when the antibiotic is given by mouth. It


is



most


apt


to


occur


in


people


with


a


history


of


allergy,


or


a


record


of


sensitivity to penicillin. Very small amounts of



penicillin, even the traces


which get into the milk of cows for a few days after they are treated with


the antibiotic for



mastitis, may be sufficient to sensitize; hence, the strong


campaign by food and drug officials keeps such milk off the



market.



To


minimize


the


risk


of


anaphylactic


shock


in


illnesses


where


injections of penicillin are the preferred treatment, a



careful doctor will


question the patient carefully about allergies and previous reactions. In


case


of


doubt


another



antibiotic


will


be


substituted


if


feasible,


or


other


precautionary measures will be taken before the injection is given.



Other


untoward


reactions


to


antibiotics


are


gastrointestinal


disorders—such


as


sore


mouth,


cramps,


diarrhea,


or


anal



itch—which


已经确定的是,对抗生素耐药的细菌< /p>


菌株的增加直接与在给定位置使用抗生素


的持续时间和程度相关。 在一家医院进行


的一项调查显示,在红霉素被广泛使用之


前,所 有从患者和人员中获得的葡萄球菌


菌株对其作用敏感。当医院开始广泛使用


红霉素时,耐药葡萄球菌菌株开始出现。



细菌耐药 性的发展可以通过更加区分


使用抗生素来最小化,服用这种药物的人

可以在这里帮助。


当必须使用抗生素时,



止抗药性发展的最好方法是尽可能迅速彻


底地消灭感染。


理想情况下,


这需要一种杀


菌药物,而不是一种抑制抑制药物 的杀菌


药物。


只要有必要彻底根除感染,


必须服用


足够的药物。


当然,


医生必 须选择药物,



即使在所有药丸消失之前症状似乎消失,


患者仍然可以通过确保服用医生推荐的整


个治疗过程来提供帮助。在极 少数情况下,


抵抗的出现可以通过抗生素的组合来延迟


或减少。 单独使用链霉素治疗结核病会导


致高度的耐药性,但是如果对氨基水杨酸


或异烟肼与链霉素一起使用,则会出现这


种并发症的可能性大大降低。



在医院治疗严重感染时,在开始治疗


之前,在 实验室中确定感染生物对适当抗


生素的敏感性。这使医生能够选择最有效


的药物或药物


;


它决定了抗生素是否对手边

< p>
的细菌具有杀菌或抑菌作用


;


它提示了完全


消灭细菌生长所需的量。


在医院或家中,


无< /p>


菌措施可以通过预防交叉感染和生物体的


扩散来帮助减少耐药菌株 的流行。



每一种抗生素都对某些人有潜在危

< br>险。他们的使用可能会导致一些严重的反


应。


一种是严重 的,


有时是致命的,


类似休


克的过敏反 应,可能会引起对青霉素敏感


的人。


口服抗生素时,

< p>
过敏反应发生频率较


低,


严重程度较轻。


最容易发生在有过敏史


或对青霉素有敏感记录的人群中。非常少


量的青霉素,甚至在用抗生素治疗乳腺炎


之后进入母牛乳中几天的痕迹可 能足以致


敏。


因此,


食品和药物官员的 强力运动使这


种牛奶不在市场上。



为 了尽量减少注射青霉素是首选治疗


的疾病过敏性休克的风险,谨慎的医生会


仔细询问病人有关过敏和以前的反应。如


果有疑问,


如果可行,


另一种抗生素将被替


代,或在注射前采取其他预防措 施。



对抗生素的其他不良反应是使用四环



occur most frequently after


use of the tetracycline group but have also


been encountered after use of penicillin



and streptomycin. These reactions


may result from suppression by the antibiotic of bacteria normally found


in the



gastrointestinal tract. With their competition removed, antibiotic-


resistant staphylococci or fungi, which are also normally



present, are free


to flourish and cause what is called a super- infection. Such infections can


be extremely difficult to cure.



A


few


antibiotics


have


such


toxic


effects


that


their


usefulness


is


strictly


limited.


They


include


streptomycin


and



dihydrostreptomycin,


which sometimes cause deafness, and chloramphenicol, which may injure


素组后最频繁出现的胃肠疾病



- < /p>


例如口


疮,


痉挛,


腹泻或肛门瘙痒,


但在使用青霉


素和链霉素后也遇到过。这些 反应可能是


由抗生素抑制胃肠道中正常发现的细菌引


起的。


通过消除竞争,


抗生素抗性葡萄球菌


或真菌


(通常也存在)


可以自由繁殖并引起


所 谓的超感染。这种感染可能极难治愈。



一些抗生素有这样的毒 性作用,它们


的用途是严格限制的。它们包括有时引起


耳聋的链 霉素和二氢链霉素,以及可能伤


the


bone


marrow.


Drugs


with


such



serious


potential


dangers


as


these


should be used only if life is threatened and nothing else will work. All


the possible



troubles that can result from antibiotic treatment should not


keep anyone from using one of these drugs when it is clearly



indicated.


Nor should they discourage certain preventive uses of antibiotics which


have proved extremely valuable.




害骨髓的氯 霉素。只有在生命受到威胁的


情况下才能使用这类具有如此严重潜在危

< br>险的药物,


否则就不能起作用。


在抗生素治


疗中可能产生的所有可能的麻烦都不应该


使任何人在使用这些药物时明确指出 。他


们也不应该阻止某些已被证明非常有价值


的抗生素的预防性 用途。






Discovery of Insulin, and the Making of a


Medical Miracle



Background



Insulin is a hormone that regulates the amount of glucose (sugar)


in the blood and is required for the body to function normally. Insulin


is


produced


by


β-cells


in


the


pancreas,


also


called


the


islets


of


Langerhans. These cells continuously release a small amount of insulin


into the body, but release surges of the hormone in response to a rise


in the blood glucose level.



Certain cells in the body change the food ingested into energy, or


blood glucose, that cells can use. Every time a person eats, the blood


glucose rises. Raised blood glucose triggers the cells in the islets of


Langerhans to release the necessary amount of insulin. Insulin allows


the blood glucose to be transported from the blood into the cells. Cells


have an outer wall, called a membrane, which controls what enters and


exits the cell. Researchers do not yet know exactly how insulin works,


but they do know insulin binds to receptors on the cell membrane. This


activates a set of transport molecules so that glucose and proteins can


enter the cell. The cells can then use the glucose as energy to carry out


its functions. Once transported into the cell, the blood glucose level is


returned to normal within hours.



Without insulin, the blood glucose builds up in the blood and the


cells are starved of their energy source. Some of the symptoms that


may


occur


include


fatigue,


constant


infections,


blurred


eye


sight,


numbness, tingling in the hands or legs, increased thirst, and slowed


healing of bruises or cuts. The cells will begin to use fat, the energy


source stored for emergencies. When this lasts for too long a time the


body produces ketones, chemicals produced by the liver. Ketones can


poison


and


kill


cells


if


they


build


up


in


the


body


over


an


extended


period of time. This can lead to serious illness and coma.



People who do not produce the necessary amount of insulin have


diabetes. There


are


two


general


types


of


diabetes. The


most


severe


type, known as Type or juvenile-onset diabetes, is when the body does


not


produce


any


insulin,


Type


I


diabetics


usually


inject


themselves


with different types of insulin three to four times daily. Dosage is taken


based


on


the


person's


blood


glucose


reading,


taken


from


a


glucose


meter.


Type


n


diabetics


produce


some


insulin,


but


it


is


either


not


enough or their cells do not respond normally to insulin. This usually


occurs in obese or middle aged and older people. Type II diabetics do


not necessarily need to take insulin, but they may inject insulin once


or twice a day.



胰岛素的发现和医学奇迹的建立



背景



胰岛素是一种调节血液中葡萄糖


(糖)



量的激素,

< br>是人体正常功能所必需的。


胰岛素


由胰腺中的

< p>
β


细胞产生,也称为朗格罕氏胰


岛。这些细胞不断 释放少量的胰岛素进入人


体,但随着血糖水平的升高而释放激素的激

增。



体内的某些细胞会将摄入的食物转化为


细胞可以利用的能量或血糖。


每人一吃,


血糖


就会升高。


升高的血糖引发朗格汉斯胰岛中的


细胞释放必要量的胰岛素。


胰岛素允许血液从


血液运输到细胞。 细胞有一个外壁,称为膜,


它控制着什么进入和离开细胞。


研究 人员尚不


清楚胰岛素是如何工作的,


但他们知道胰岛素


与细胞膜上的受体结合。


这激活了一组转运分


子 ,


使葡萄糖和蛋白质可以进入细胞。


然后细

胞可以使用葡萄糖作为能量来执行其功能。



旦运送到细胞 中,


血糖水平在数小时内恢复正


常。



如果没有胰岛素,


血液中的血糖会积聚在


血液中,


细胞就会缺乏能量来源。


可能发生的


一些症状包括疲劳,感染持续,视力模糊,手


脚麻木,


手脚刺痛,


口渴增加,


伤口愈合减慢。


细胞将开始使用脂肪,紧急情况下储存的能


源。当这种持续时间太长时,身体会产生酮,


肝脏产生的化学物质。


如果酮在体内长时间累

< br>积,


酮可以毒杀细胞。


这可能导致严重的疾病

< p>
和昏迷。



不产生必需量的胰岛素的人患有糖尿病 。


有两种一般类型的糖尿病。


最严重的类型,

< br>即


类型或青少年型糖尿病,


是当身体不产生任何


胰岛素时,


I


型糖尿病患者通常每天注射不同< /p>


类型的胰岛素三至四次。


根据从葡萄糖计取得

的人的血糖读数来服用剂量。



n


型糖尿病患者


会产生一些胰岛素,


但这或者是不够的,


或者


他们的细胞对胰岛素没有正常的反应。


这通 常


发生在肥胖或中年人和老年人。



I I


型糖尿病


患者不一定需要服用胰岛素,


但可以每天注射


一次或两次胰岛素。



胰岛素几乎没有被发现



在发现胰岛素 之前,


糖尿病是一种可怕的


疾病,最可能导致死亡。病人浪费了 ,变得虚


弱,


在不可避免的死亡之前难以形容。


他们渴


望饥渴,


但饥饿只是让事情变得更糟,


继续减


肥。医生知道,糖会加重糖尿病患者的病情,

How Insulin Almost Wasn't Discovered



Before the discovery of insulin, diabetes was a feared disease that


most


certainly


led


to


death.


Patients


wasted


away,


grew


weak,


and



suffered


indescribably


before


their


inevitable


death.


They


had


insatiable


thirst


and


hunger,


but


trying


to


satisfy


their


hunger


only


made things worse, and they continued to lose weight. Doctors knew


that sugar worsened the condition of diabetic patients and that the most


effective treatment was to put the patients on very strict diets where


sugar intake was kept to a minimum. At best, this treatment could buy


patients a few extra years, but it never saved them. In some cases, the


harsh diets even caused patients to die of starvation.



During the nineteenth century, observations of patients who died


of diabetes often showed that the pancreas was damaged. In 1869, a


German


medical


student,


Paul


Langerhans,


found


that


within


the


pancreatic tissue that produces digestive juices there were clusters of


cells


whose


function


was


unknown.


Some


of


these


cells


were


eventually shown to be the insulin- producing beta cells. Later, in honor


of the person who discovered them, the cell clusters were named the


islets of Langerhans.



In


1889


in


Germany,


physiologist


Oskar


Minkowski


and


physician


Joseph


von


Mering,


showed


that


if


the


pancreas


was


removed from a dog, the animal got diabetes. But if the duct through


which the pancreatic juices flow to the intestine was ligated-surgically


tied


off


so


the


juices


couldn't


reach


the


intestine-the


dog


developed


minor


digestive


problems


but


no


diabetes.


So


it


seemed


that


the


pancreas must have at least two functions:



?


To produce digestive juices



?


To produce a substance that regulates the sugar glucose.



This hypothetical internal secretion was the key. If a substance


could actually be isolated, the mystery of diabetes would be solved.


Progress, however, was slow.



In 1920, an unknown Canadian surgeon named Frederick Banting


approached


Professor


John


Macleod,


the


head


of


the


University


of


Toronto's


physiology


department,


with


an


idea


about


finding


that


secret.


He


theorized


that


the


pancreatic


digestive


juices


could


be


harmful


to


the


secretion


of


the


Pancreas


produced


by


the


islets


of


Langerhans. He therefore wanted to ligate the pancreatic ducts in order


to stop the flow of nourishment to the pancreas. This would cause the


pancreas to degenerate, making it shrink and lose its ability to secrete


the


digestive


juices.


The


cells


thought


to


produce


an


antidiabetic


secretion


could


then


be


extracted


from


the


pancreas


without


being


harmed.


Unfortunately,


Macleod,


a


leading


figure


in


the


study


of


diabetes


in


Canada,


didn't


think


much


of


Banting's


theories


and


rebuffed


his


suggestion. Despite


this,


Banting


managed


to


convince


Macleod


that


his


idea


was


worth


trying.


Macleod


gave


Banting


a


laboratory with a minimum of equipment and ten dogs. Banting also


got an assistant, a medical student by the name of Charles Best. The


experiment was set to start in the summer of 1921.



Banting


and


Best


began


their


experiments


by


removing


the


pancreas from a dog. This resulted in the following:



?



It's blood sugar rose.


< p>
最有效的治疗方法是将病人的糖摄入量控制


在非常严格的水平。

< p>
充其量,


这种治疗可以多


买几年的病人,


但从来没有挽救过。


在某些情


况下,严酷的饮食 甚至导致病人死于饥饿。



在十九世纪期间,

< br>死于糖尿病的病人的观


察结果常常表明胰脏已经受损。



1869


年,一


位德国医学学生


Paul Langerhans


发现,


在产 生


消化液的胰腺组织内,有功能未知的细胞簇。


其中一些细胞最 终被证明是产生胰岛素的


β


细胞。后来,为了纪念发现他们的人 ,细胞群


被命名为朗格汉斯岛。



18 89


年在德国,生理学家奥斯卡


·


闵可 夫


斯基(


Oskar Minkowski

)和医师约瑟夫


·



·

< p>


林(


Joseph von Mering


)发现,如果将胰脏从


狗身上取下,动物就会患上糖尿病。但是,如


果将胰液流入肠道的导管结扎在外科手术中,


使得汁液不能到达 肠道,


那么狗就会产生轻微


的消化问题,


但不会产生糖尿病。


所以胰腺似


乎至少有两个功能:



?


产生消化液



?


生产调节糖分的物质。


< p>
这个假设的内分泌是关键。


如果一个物质


实际上可 以孤立,


糖尿病的奥秘将被解决。



进 展缓慢。



1920












·



廷< /p>



Frederick Banting



的未知加拿大外科医生向


多伦多大学生理学系主任约翰


·


麦克劳德



Joh n


Macleod


)教授提供了一个关于如何找到这个


秘密的想法。


他推论胰腺消化液可能对朗格汉


斯胰岛产生的胰腺分泌有害。


因此,


他想结扎

< br>胰管,


以阻止营养物流向胰腺。


这会导致胰腺

< p>
退化,使其萎缩,失去分泌消化液的能力。认


为产生抗糖尿病分泌物的细胞 然后可以从胰


腺中提取而不受伤害。


不幸的是,


加拿大糖尿


病研究领域的领军人物麦克劳德



Macleod




班 廷的理论并没有太多的想法,


并且拒绝了他


的建议。

< p>
尽管如此,


万津设法说服了麦克劳德,


他的想法值 得尝试。


麦克劳德给班廷一个实验


室,


配备了最少的设备和十只狗。


班廷还找到


了一位名叫查尔斯


·


贝斯特的医学助理。实验


定于

< p>
1921


年夏天开始。



万津和最好的开始他们的实验,


从狗取出


胰腺。这导致了以下结 果:



?



血糖升高



?



口渴,多喝水,多喝水。



?



变得越来越弱对另一只狗进行试验 ,万


津和贝佳手术结扎胰腺,停止营养的流


动,使胰腺退化。过 了一段时间,他们



?



It became thirsty drank lots of water, and urinated more often.



?



It


became


weaker


and


weaker


Experimenting


on


another


dog,


Banting


and


Best


surgically


ligated


the


pancreas,


stopping


the


flow


of


nourishment,


so


that


the


pancreas


degenerated. After


a


while, they removed the pancreas, sliced it up and froze the pieces


in a mixture of water and salts. When the pieces were half frozen,


they


were


ground


up


and


filtered.


The


isolated


substance


was


named “isletin”.



The extract was injected into the diabetic dog. Its blood glucose


level


dropped,


and


it


seemed


healthier


and


stronger.


By


giving


the


diabetic dog a few injections a day, Banting and Best could keep it


healthy and free of symptoms. Banting and Best showed their result to


Macleod, who was impressed but he wanted more tests to prove that


their


pancreatic


extract


really


worked.


For


the


increased


testing,


Banting and Best realized that they required a larger supply of organs


than their dogs could provide, and they starred using pancreases from


cattle. with this new source, they managed to produce enough extract


to


keep


several


diabetic


dogs


alive.


The


new


results


convinced


Macleod that they were onto something big. He gave them more funds


and moved them to a better laboratory with proper working conditions.


He also suggested that they should call their extract


work


proceeded


rapidly.


In


late1921,


a


third


person


biochemist


Bertram Collip, joined the team. Collip was given the task of trying


topuri4


the


insulin


so


that


it


would


be


clean


enough


for


testing


on


humans. During the intensified testing, the team also realized that the


process


of


shrinking


the


pancreases


had


been


unnecessary.


Using


whole fresh pancreases from adult animals worked just as well.



In 1922 the insulin was tested on Leonard Thompson, a 14-year-


old diabetes patient who lay dying at the Toronto General Hospital. He


was given an insulin injection. At first he suffered a severe, allergic


reaction and further injections were cancelled. The scientists worked


hard on improving/ the extract and then a second dose of injections


were


administered


on Thompson. The


results


were


spectacular. The


scientists went to the other wards with diabetic children, most of them


comatose and dying from diabetic keto-acidosis. They reacted just as


positively as Leonard to the insulin extract.



Banting and Macleod were awarded the Nobel Prize in 1923 for


the practical extraction of insulin. They were incensed that the other


members of their team were not included, and they immediately shared


their prize money with Best and Collip. They sold the original patent


to the University of Toronto for one half dollar. They were not looking


for


fame


or


fortune;


they


wanted


to


keep


sick


children


from


dying.


They did eventually benefit financially, but that was the last thing on


their minds.



Very soon after the discovery of insulin, the medical firm Eli Lilly


started large-scale production of the extract. As early as in 1923, the


firm


was


producing


enough


insulin


to


supply


the


entire


North


American continent. Although insulin doesn't cure diabetes, it's one of


将胰脏切除,将其切片并冻结在水和盐


的混合物中。当冰 块半冻时,将其磨碎


并过滤。分离的物质被命名为“通


报”。< /p>



将提取物注射到糖尿病狗中。


其血糖水 平


下降,


似乎更健康和更强。


通过给糖 尿病狗每


天注射几次,


Banting



Best


可以保持健康和


没有症状。



Banting


< br>Best


向麦克劳德展示了


他们的成果,


他对此印象深刻,


但他想要进行


更多的测试来证明他们 的胰脏提取物确实有


效。为了增加测试,


Banting



Best


认识到他


们需要比他们的狗能够提供更多的器官供应,


并且他们使用来自牛的胰脏来主演。


有了这个


新的来源,


他们设法产生足够的提取 物,


让几


只糖尿病的狗保持活着。


新的 结果使麦克劳德


相信他们正在做一些大事。


他给了他们更多的< /p>


资金,


把他们搬到了一个有适当工作条件的更

好的实验室。


他还建议,


他们应该叫他们的提


取物



胰岛素


< p>


现在,


工作进展迅速。



1921


年底,第三人称生物化学家


Bertram


Collip



入了 队伍。



Collip


被赋予尝试


topuri4


胰岛素


的任务,

< p>
以便它足够干净,


可以在人体上进行


测试。


在加强检测过程中,


团队也意识到缩小


胰腺的 过程是不必要的。


使用来自成年动物的


全新鲜的胰腺也同样如此 。



1922


年,在

< br>14


岁的多伦多综合医院死亡




尿




者< /p>





·





< p>
Leonard


Thompson


< p>
身上测试了胰岛素。


他被给了胰岛


素注射。起初, 他遭受了严重的过敏反应,取


消了进一步的注射。科学家努力改善


/


提取物,


然后在汤普森进行第二次注射。结果是壮观


的。科学家去了另一个病房与糖尿病的孩子,


他们大多是昏迷和死于糖 尿病酮酸中毒。


他们


的反应和


Leon ard


一样积极。



万津和麦克劳德在


1923


年被授予诺贝尔


奖,用于实际 提取胰岛素。他们被激怒,其他


队员不包括在内,


他们立即用< /p>


Best



Collip



享他们的奖金。


他们把原来的专利卖给了多伦


多大学半美元。


他们不是为了名利,


他们想让


生病的孩子免于死亡。他们最终在经济上受


益,但这是他们心中 的最后一件事。



在发现胰岛素后不久,医药公司


Eli


Lilly


就开始大规模生产提取物。早在


1923


年,该


公司就生产出足够的胰岛素供应整个北美大


陆。


虽然胰岛素不能治愈糖尿病,


但这是医学


界最大的发现之一。


一旦到来,


就像是一个奇


迹。


患有严重糖尿病,


只剩下几天生活的人得< /p>



the


biggest


discoveries


in


medicine.


When


it


came,


it


was


like


a


救了。


只要不断得到胰岛素,


他们就能过上几


miracle . People with severe diabetes and only days left to live were


乎正常的生活。



saved. And as long as they kept getting their insulin, they could live an


使用人胰岛素



almost normal life.



1982


年,礼来公司生产了一种人胰岛素


Working with human insulin




Humulin?




成为首个获得批准的基因工程


In


1982,


the


Eli


Lilly


Corporation


produced


a


human


insulin < /p>


药物产品。


这一重要成就是


20


世纪


50


年代由


(Hu mulin?)


that


became


the


first


approved


genetically


engineered


沃森和克里克对


DNA


进行的经典结构研究以


pharmaceutical product. This important achievement was the result of


及由桑格公司提供的胰岛素开始的一个广泛


a vast network of basic and applied scientific advances that began in


的基础和应用科学进展网络的结果。

研究人员


the 1950s with the classic structural studies on DNA by Watson and


Crick


and


on


insulin


by


Sanger.'


Without


needing


to


depend


on


animals, researchers could produce genetically engineered insulin in


unlimited


supplies.


It


also


did


not


contain


any


of


the


animal


contaminants. Using human insulin also took away any concerns about


transferring


any


potential


animal


diseases


into


the


insulin.


While


companies


still


sell


a


small


amount


of


insulin


produced


from


animals—mostly


porcine—from


the


1980s


onwards,


insulin


users


increasingly


moved


to


a


form


of


human


insulin


created


through


recombinant DNA technology.



Insulin


is


a


protein


consisting


of


two


separate


chains


of


amino


acids, an A above a B chain, that are held together with disulfide bonds.


The insulin A chain consists of 21 amino acids and the B chain has 30.


Before becoming an active insulin protein, insulin is first produced as


preproinsulin. This is one single long protein chain with the A and B


chains


not


yet


separated,


a


section


in


the


middle


linking


the


chains


together and a signal sequence at one end telling the protein when to


start secreting outside the cell. After preproinsulin, the chain evolves


into proinsulin, still a single chain but without the signaling sequence.


Then comes the active protein insulin, the protein without the section


linking the A and B chains. At each step, the protein needs specific


enzymes to produce the next form of insulin.



Lilly


has


prepared


human


insulin


by


two


different


means'


initially,


by


a


chain


combination


procedure


and,


since


1986,


by


transforming human proinsulin into human insulin. In the first method,


the two insulin chains are produced separately. Manufacturers need the


two mini-genes: one that produces the A chain and one for the B chain.


Since the exact DNA sequence of each chain is known, they synthesize


each


mini- gene's


DNA


and


insert


them


into


plasmids.


The


recombinant,


newly


formed,


plasmids


are


then


transformed


into


bacterial cells. During a fermentation process, the millions of bacteria


harboring the recombinant plasmid replicate roughly every 20 minutes


through


cell


division,


and


each


expresses


the


insulin


gene.


After


multiplying,


the


cells


are


taken


out


of


the


fermentation


tanks


and


broken


open


to


extract


the


protein


chains. The


two


chains


are


then


mixed together and joined by disulfide bonds through the reduction-


reoxidation


reaction.


Although


the


chain


combination


procedure


worked quite well, the proinsulin approach required fewer processing


不需要依 赖动物,


就可以生产出无限制供应的


基因工程胰岛素。


它也没有包含任何动物污染


物。


使用人体胰岛素 也消除了将任何潜在动物


疾病转移到胰岛素中的担忧。尽管从


2 0


世纪


80


年代开始,


公司仍然出售少量由动物产生的


胰岛素(主要是猪),但是胰岛素使用者越来< /p>


越多地转向通过重组


DNA


技术形成的人 胰岛


素形式。



胰岛素是一种蛋白质,


由两条独立的氨基


酸链组成,一条


B< /p>


链以上的


A


链与二硫键结


合在一起。胰岛素


A


链由


21


个氨基酸组成,


B


链有


30


个。


在成为活性胰岛素蛋白质之前,


胰岛素首先作为前胰岛素原产生。


这是一个单


链长的 蛋白质链,


A


链和


B

< br>链还没有分开,



间的一段链接在一起,


信号序列的一端告诉蛋


白质何时开始在细胞外分泌。前胰岛素原后,

< p>
链发展成胰岛素原,


仍然是单链,


但没有信号


序列。然后是活性蛋白质胰岛素,不含连接


A



B


链的部分的蛋白质。


在每个步骤 中,


蛋白


质都需要特定的酶来产生下一种形式的胰岛

< p>
素。



礼来公司通过两种不同的方式来制备人


胰岛素



-


最初 是通过链式结合的方法,自


1986


年以来,

< br>通过将人胰岛素原转化成人胰岛


素,


第一种方法是分别生 产两种胰岛素链,



因:一个产生


A< /p>


链和一个


B


链,由于每条链


的确切的


DNA


序列是已知的,他们合成每个


小基因的


DNA


并将它们插入到质粒中,然后


转化新形成的重组质粒在发酵过程中,


携带重

< br>组质粒的数百万个细菌通过细胞分裂大约每



20


分钟复制一次,每个细胞表达胰岛素基



;


倍增后,将细胞从发酵罐中取出,打开提


取蛋白质链,


然后将两条链混合在一起,


通过


还原

< p>


-


再氧化反应通过二硫键连接,尽管链


组合过程起作用胰岛素原方法需要较少的处


理步骤,因此在

< p>
1986


年取代了链式方法。将


编码胰岛素原的序 列插入到非致病性大肠杆


菌细菌中。


细菌经过发酵过程,


再生产胰岛素

-


-


-


-


-


-


-


-



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