人体生理学 (1).pdf
William Harvey was born to a reasonably well-to-do fam-ily during a period of unparalled intellectual fervor.Theyear was 1578,and the period has come to be known as theperiod of the“scientific revolution.”And indeed,it was a rev-olution,not because of the frequency of scientific discoveries that prize goes to the present but because it witnessed arevolution in epistemological thinking,an upheaval in theapproach to acquiring the truth about the natural world.But more about that later.Because of his family status,Harvey had no problemobtaining a privileged education.He studied at the elite KingsSchool in Canterbury(1588?1594)and later at Gonville andCaius College of Cambridge University,where he received aB.A.He obtained a Doctor of Physic diploma from the Uni-versity of Padua in 1602.That institution,the alma mater of thesame Dr.Caius who helped found Harveys alma mater atCambridge,was one of the great centers of medical educationat the time,the home of Galileo and the great anatomist Ver-salius.There Harvey studied under a student of Versalius,Fabricius,who had written a treatise on the valves in veins buthadnt the vaguest idea about what they did other than thatthey might slow blood flow(6,13,14,17).Years later,when Harvey was close to death,he was askedby Robert Boyle what had induced him to think that the bloodcirculated(13,17).Harvey replied.that when he took notice the Valves in the Veins of somany several parts of the body,were so placd that theygave free passage to the Blood Towards the Heart,butopposd the passage of the Venal blood the Contrary way:He was invited to imagine that so Provident a Cause asNature had not so Placd so many Valves without Design:and no Design seemd more probable,than That,sincethe Blood could not well,because of the interposingValves,be Sent by the Veins to the Limbs;it should beSent through the Arteries and Return though the Veins,whose Valves did not oppose its course that way.(4)After returning to London,Harvey obtained his M.D.degreefrom Cambridge(1602);he became a Fellow of the Royal Col-lege of Physicians in 1607 and the physician to St.Bartholomews Hospital in London in 1609.Later,at the ageof 37,he was appointed to the distinguished position of Lum-leian Lecturer in anatomy at the College of Physicians.It wasin the latter capacity that he undertook the experiments thatwere to lead to one of the greatest scientific revolutions of thecentury one that was to abolish,without a trace,a dogmathat had persisted for almost 1,500 years(11,12,14).The origin of GalenismTo fully appreciate the magnitude of Harveys revolution,we have to dip back in time to the golden age of Greece,around 400 B.C.By that time,the Hellenist civilization hadrejected the mythological notions of earlier civilizations thatplaced everyday events in the hands of spirits in favor of theconviction that events such as rain or disease have naturalrather than supernatural causes and that these causes are sub-ject to critical and rational analysis:a transition from“mythos”to“logos,”from mythology to logic or reason(14).Accordingly,humans were believed to be made up of thesame fundamental elements(Fig.1)that comprise all of thecosmos fire,water,air,and earth.Furthermore,these ele-ments could have the qualities of being hot,cold,dry,and/ormoist.The food and drink that animals consumed consisted ofthese elements,and in the course of digestion they were con-verted into the bodily juices or humors,namely the blood,phlegm,yellow bile,and black bile,respectively.From thesecame the descriptors sanguine,phlegmatic,choleric,andmelancholic(11,14).Hippocrates(1,14),considered the founder of Westernmedicine,maintained that health required the proper balanceof these elements;imbalance resulted in disease.Thus,in asense,Hippocrates and the school of medicine that followedhim can be considered the originators of the notion of“home-ostasis.”Almost two millennia later,this notion was reinventedby Claude Bernard to describe the constancy or fixit of theinternal environment or milieu interior necessary for a free andindependent life(2),and the term“homeostasis”was formallyintroduced into the scientific literature by Walter Cannon in1939 in his great book entitled The Wisdom of the Body(5).When one reads the treatises that bear Hippocrates name,for many of these treatises are believed to have been writtennot by him but by his followers(1),one is impressed by the175William Harvey and the Circulation of the Blood:The Birth of a Scientific Revolution and ModernPhysiologyStanley G.SchultzDepartment of Integrative Biology and Pharmacology,University of Texas Medical School,Houston,Texas 77225 HISTORICAL PERSPECTIVENEWS IN PHYSIOLOGICAL SCIENCES0886-1714/02 5.00 2002 Int.Union Physiol.Sci./Am.Physiol.Soc.News Physiol Sci 17:175?180,2002;www.nips.org10.1152/nips.01391.2002clinical acumen in the face of a nearly complete ignorance ofthe relation of disease to the structure and function of thehuman body.What remains of Hippocrates today is his“oath”(1);the physicians“Sermon on the Mount,”intended to initi-ate them into one of mans noblest professions.The Hippocratic school dominated Western medicine forthe next 500 years,until another Greek came onto the scene,namely Galen,who was born in what is now Turkey but spentmost of his adult life and rose to medical fame in Rome(14,15).Galen built on the earlier Hippocratic concept thathuman health required an equilibrium between the four mainbodily fluids or humors but regarded anatomy as the founda-tion of medical knowledge and did many dissections on loweranimals(15);he also served for a short time as the physicianto a school of gladiators and so must have seen the humanbody in various forms of gory disarray(15).In contrast withHippocrates,he felt that health depended on the proper bal-ance of humors in specific organs,not only the body as awhole.Galen viewed the body as consisting of three connectedsystems(Fig.2):the brain and nerves,which were responsiblefor sensation and thought;the heart and arteries,which wereresponsible for life-giving energy or“vital spirit”;and the liverand veins,which were responsible for nutrition and growth.According to Galen,blood was formed in the liver from foodcarried to that organ from the stomach and intestines via theportal vein.This“natural”blood then entered the systemicveins and was carried to all parts of the body,by an ebb andflow,where it was consumed as nutrient or was transformedinto flesh.Thus blood was not conserved;it was constantlybeing consumed in the periphery and replenished by ingestednutrients,and this was all carried out by the right ventricle andgreat veins.The main task of the left ventricle was to generate a pulsatileforce to blood in the arteries,which absorbed“pneuma”orspirit from the lungs.Much of the blood in the left ventriclecame directly from the right ventricle through pores in theinterventricular septum and some through“leaks”in the pul-monary circulation;the latter were needed to explain the factthat the pulmonary veins contained blood and were not filledwith air alone.The main purpose of the“vital”arterial blood,as distinguished from the“natural”venous blood,was todeliver pneuma or“spiritus vitalus”to the peripheral tissues.According to Galen,there was little mingling between arterialand venous blood;each stream had its distinct and essentialpurpose.In this sense,Galen was a true post-Aristotelian whoblended a touch of empiricism,in this case anatomic findings,with a large dose of causal or teleological speculation;every-thing had to serve a purpose or final cause.All parts of the human body are formed in the optimalmanner to serve their intended human purposes.Natureis provident,just,and all knowing and does nothing invain.(15)In the case of the functions of the heart and great vessels,Galens model was biased by the heavy emphasis the Greeksplaced on the role of a wholesome diet and fresh air in pre-serving health.Thus the function of the right side of the vas-culature was to deliver the products of a healthy diet to the tis-sues of the body and that of the left side was to deliver freshair and cool the body.This model was to survive,essentially unquestioned,for thenext 1,400 years despite the fact that some had denied,andno one had been able to confirm,the presence of holes in theinterventricular septum(see below).In the absence of suchcommunications there should be little blood in the arteries,and that was contrary to innumerable observations.But whylet dirty facts blemish what appeared to be a nice theory?Thefact that the model provided an explanation for the existenceof certain anatomic structures that was consistent with“Natures”purported intent was enough;experimentation wasunnecessary!The demise of Galenism and the birth of a new para-digmAs pointed out above,Harvey was well trained in anatomy,and he,like his idols Versalius and Fabricius,was convincedthat the interventricular septum was not leaky to blood.Inaddition,he was born into an era in which experimentation(the use of the hands)and computation,in addition to simpleobservation,became recognized as essential tools of the“sci-entific method.”He was well aware of the work of Copernicusand Kepler,who preceded him,and of his contemporaryNews Physiol Sci Vol.17 October 2002 www.nips.org176FIGURE 1.The relations among the elements that comprise the universe,theirqualities,and the humors present in the human according to the ancientmodel.Galileo,for whom the combination of careful observation andcomputation resulted in nothing less than a switch betweenthe earth and the sun as the center of our universe;Galileosdictum“Measure all that is measurable,and make thosethings measurable which have hitherto not been measured”(13)was deeply impressed upon him.He was also familiarwith the somewhat earlier writings of Santorio Santoro,who,sitting on an exquisitely sensitive balance,compared his bodyweight and the difference between the ingested food and hisexcreta and was capable of observing that the body lost a cer-tain amount of weight continuously in the form of“insensibleperspiration”(14).But Harvey himself was a pioneer who had no footsteps tofollow(11).Unlike the great Kepler,who improved uponCopernicus observations,and Galileo,whose telescopeunequivocally established the Copernican revolution,Harveydid not build on anything,revise anything,or improve on any-thing.Instead,he eradicated an existing dogma without atrace and replaced it with a paradigm whose essential featuresare immutable.It remains today the greatest“single-handed”discovery inphysiology and medicine,if not science in general.This revolution was set forth in an exquisitely written 70-page monograph entitled“Exercitatio Anatomica de MotuCordis et Sanguinis in Animalibus”or“Anatomical Essay onthe Motion of the Heart and Blood in Animals”(7,8),com-monly referred to as“De Motu Cordis”or simply“De Motu.”It was published in 1628 when Harvey was already 50 yearsold.Knowing that he was challenging a“big fish,”albeit at firstunintentionally,he opened the monograph with a letter to theKing,Prince Charles,with the statement The heart of animals is the foundation of their life,thesovereign of everything within them.from which allpower proceeds.The King,in like manner,is the founda-tion of his kingdom,the sun of the world around him,theheart of the republic,the foundation whence all power,all grace doth flow.(8)His dedication to the President of the Royal College of Physi-cians reads like:“Hey,Im really not out to get anyone,all Iwant to do is tell the truth!”For example,in this“dedication”he states.the studious and good and true do not esteem it dis-creditable to desert error,though sanctioned by the high-est antiquity,for they know full well that to err,to bedeceived,is human.I would not charge with willfulfalsehood any one who was sincerely anxious for truth,nor lay it at any ones door as a crime that he had falleninto error.I avow myself the partisan of truth alone.(8)He closes:“Farewell,most worthy Doctors,and think kindlyof your Anatomist”(8),suggesting that he feared the worst.Harveys revolutionary conclusion that blood is conservedand circulates was based on only a few observations.Themajor ones were as follows.First,he measured the total amount of blood that could bedrained from sheep,pigs,and some other subprimate mam-mals.He then measured the volume of the left ventricles ofthese animals and calculated that,if the left ventricle were toempty with each beat,in one hour the total volume of bloodpumped would be much greater that in the ingesta or eventhat contained in the entire animal.Indeed,this would be trueeven if one-tenth of the blood contained by the ventricle wereejected per beat.Therefore,he concluded,“.it is a matter ofnecessity that the blood perform a circuit,that it returns towhence it set out.”He then demonstrated,publicly,that when a live snake is“laid open,”compression of the vein entering the heart leadsto a small heart that is devoid of blood upon opening it.If on the contrary,the artery instead of the vein be com-pressed or tied you will observe the part between theobstacle and the heart,and the heart itself to becomeinordinately distended and,at end,to become sooppressed with blood that you will believe it about to bechoked.(8)News Physiol Sci Vol.17 October 2002 www.nips.org177FIGURE 2.Galens view of physiological systems,particularly the heart andgreat vessels.Note the communication between the right and left ventriclesand the independent flows taking place in the venous and arterial vessels.He also showed that,following light application of a tourni-quet to the arm(Fig.3),the veins become engorged and thatblood can only be milked from an engorged vein in the oraldirection toward the heart but when the vein is thusemptied it only fills from the periphery.Furthermore,knowingthe diameter and length of the cylinder of vein,one can cal-culate the volume of blood that flows through the vein duringrapid emptying and refilling.Harvey showed that in a daymore blood flows through that segment alone than the quan-tity of food ingested.If the tourniquet is rapidly applied very tightly,as was thepractice in preparation for amputation,the arm blanches andveins do not become engorged.Thus veins are filled by arter-ies.Just how they were filled puzzled Harvey,but not enoughfor him to question the truth of his conclusion.He postulatedthe existence of small capillary anastomoses between arteriesand veins,but these were not discovered until 1661,a fewyears after Harvey died,by Marcello Malpighi while studyingthe lungs of frogs(11).Why did Galens model dominate for 1,400 years?An examination of the transition between the Galenicmodel of the circulation of the blood and the Harveian modelsheds some light on the nature of the progress of science or,more exactly,on scientific revolutions.Why in heavens name did the Galenic model last almost1,400 years?It was obviously baseless.Many anatomists,including the great Leonar
