Spinoza Lectures: Constituents of Life by John Dupré

8/4/2019 Spinoza Lectures: Constituents of Life by John Dupr

1/28

The ConsTiTuenTsof Life

John Dupr


2/28

The

ConsTiTuenTsof Life

John Dupr

Spinoza Lectures

Will Kymlicka - States, Natures and CulturesISBN 90 232 3224 0

Manred Frank - Selbstbewutsein und ArgumentationISBN 90 232 3278 X

Richard Rorty - Truth, politics and post-modernismISBN 90 232 3279 8

Albrecht Wellmer - Revolution und InterpretationISBN 90 232 3426 X

Axel Honneth - Suffering from IndeterminacyISBN 90 232 3564 9

Seyla Benhabib - Transformations of CitizenshipISBN 90 232 3724 2

Hilary Putnam - Enlightenment and PragmatismISBN 90 232 3739 0

Judith Butler - Giving an Account of OneselfISBN 90 232 3940 7

Nancy Fraser - Reframing JusticeISBN 90 232 4155 X

Hubert Dreyus - Skilled Coping as Higher Intelligibility in HeideggersBeing and TimeISBN 978 90 232 4378 6

John Dupr - The Constituents of LifeISBN 978 90 232 4380 9

2007


3/28

TabLeof ConTenTs

Acknowledgement 7

Spinoza Lecture I 9

Spinoza Lecture II 33

John Dupr

All rights reserved. No part o this publication may be reproduced, stored in

a retrieval system, or transmitted, in any orm or by any means, electronic,

mechanical, photocopying, recording, or otherwise, w ithout the prior permis-

sion o the Publisher.

ISBN 978 90 232 4380 9

The Department o Philosophy o the University o Amsterdam presented the

Spinoza Lectures by John Dupr in May and June 2006.

Design: Anneke de Bruin, Amsterdam

Cover: Crasborn, Valkenburg a.d. Geul

Printing: Royal Van Gorcum, Postbus 43, 9400 A A Assen


4/28

aCknowLedgemenT

This book is a slightly revised version o the Spinoza Lecturesdelivered at the University o Amsterdam in May and June 2006. I

am very grateul to the Philosophy Department o the University oAmsterdam or giving me the opportunity to deliver the lectures andto spend a most enjoyable and productive term in that beautiul city.I would like especially to thank Proessor Frans Jacobs, Head o theDepartment, or his excellent hospitality during the visit, and RiaBeentjes and Willy van Wier or taking care o al l the practical needsconnected with my visit with exemplary eciency. Conversationswith Michiel van Lambalgen, Martin Stokho, Beate Roessler, Gerardde Vries, Veit Bader, and Tine Wilde contributed greatly to both myenjoyment and my intellectual well-being. Teaching a postgraduateseminar on Philosophy o Biology with Wolram Hinzen provided aninvaluable opportunity to discuss some o the issues with an appro-

priately sceptical audience.

The work rom which these lectures derives is greatly indebtedto many colleagues at Egenis, The Economic and Social ResearchCouncil (ESRC) Centre or Genomics in Society, with whom I havebeen discussing many o t he issues addressed or several years, mostespecially Barry Barnes, Steve Hughes, Christine Hauskeller, StaanMueller-Wille, Lenny Moss, Paula Saukko and Jane Calvert. Mucho the work presented here derives rom research undertaken there,and I am very grateul to the ESRC or its continuing support. Mygreatest individual debts are to Maureen OMalley, with whom I havebeen collaborating or some time on philosophical topics in micro-biology and systems biology, and without whose expertise and insighton those topics I would not have been able to write these lectures;and to Regenia Gagnier, who as always read and provided uniquelyinsightul comments on drats o the work, and whose stimulationand encouragement is an essential background to all my philosophi-cal work.


5/28

Spinoza Lecture i

The

ConsTiTuenTs

of Life


6/28

11

First Lecture

The title o these talks, The Constituents o Lie, reers to thethings that are the subject matter o biology: organisms, the systems,organs, cells and molecules to be ound within them, and the largersystems, such as species or ecosystems which they, in turn, compose.It might not be obvious that there is much or a philosopher to say on

this subject. We are all amiliar enough with these things at a com-mon sense level, but it is surely or biologists to provide us with moresophisticated insight into what these things do and how they do it.Yet attempting to provide philosophically adequate accounts o thesevarious categories has proved extremely dicult, and such di cultieshave been a major topic or my won academic specialty, the philoso-phy o biology. In these lectures I shall consider some o these kindso things and the philosophical diculties they present. A wider aimwill be to try to locate some undamental problems in our concep-tion o lie and its constituents, problems that more generally explainthese dicult ies in understanding central biological categories.

It is natural and traditional to think o lie in terms o a str ucturalhierarchy. We analyse an organism into a set o interacting organsand systems livers, hearts, brains, ci rculatory systems, immunesystems, and so on and these in turn into smaller structural com-ponents, most notably cells. Cells, in turn are understood as enor-mously complex ensembles o interacting molecules. And this pic-ture extends in both directions. Molecules are complex structures oatoms; organisms are components o species, ecological systems orsocial groups. And so on.

This vision has undeniably been undamental to the extraor-dinary success the sciences have achieved in advancing our under-standing o the natural world. This success has oten been taken tolend support to a more general reductionist scientic methodology.Reductionism, in its classical orm, is the explanation o the behav-iour o complex entities in terms o the properties o their par ts, andsome philosophers have taken this position to its logical conclusionand suggested that ultimately the world is, in principle at least, ullydescribable and intelligible in terms o the smallest microphysicalparticles it contains.


7/28

12

the constituentsoF LiFe

13

First Lecture

Reductionism has, however, been much criticised, including inthe past by mysel.1 I shall not explicitly pursue this critical projecttoday. In opposition to reductionism I have, over a number o years,deended a quite dierent, pluralistic perspective.2 According to thisperspective there are many dierent kinds o things in the world,

rom physically simple things like electrons or quarks, to very com-plex things such as planets, elephants, or armies. Many or all thesethings, in my view, have equal claims to reality. As the basis o thisposition is the idea that many or a ll such entities have causal powersthat are not simply consequences o the way their physical compo-nents are tted together. This perspective g ives biology, in particular,autonomy rom the physical sciences. One objective o these lectureswill be to explain and deend this point o view.

Let me begin by pointing out what is perhaps the deepest di-culty with the reductionist hierarchy. Contrasting with the idea thatlie consists o a hierarchy o things, we may observe that it is more

realistic to consider it as a hierarchy o processes. In a ty pical cell in ahuman body many thousands o chemical reactions are taking placeevery second. Molecules are constructed, reshaped, or dissolved. Thecells in which they reside, divide, develop, and die. All o these count-less events take place within a much longer process, the lie cycle othe organism: conception, birth, death, and an exquisitely complexsequence o stages in between. And as these lie cycles give rise to newlie c ycles through reproduction3 we begin to glimpse a much longerprocess still, evolution. This reminds us that t hese lie cycles are nota sequence o replicas but rather a sequence o similar but subtly di-erent processes, Just as the process that is the lie cycle o an organ-ism changes constantly, partly in reaction to the demands put on itby its environment, so the sequence o lie cycles changes in response

1 SeeespeciallyTheDisorderofThings:Metaphysical Foundations of the Disunity ofScience,Cambridge:HarvardUniversityPress,1993.

2 Op.ci t. See also Humans and Other Animals, Oxford:Oxford UniversityPress,2002.

3 IshouldemphasisethatbyreproductionIinclude,forthecaseoforganismssuchasourselves,muchmorethanthebiologicalprocesswhichistheprimaryrefer-entofthisterm.FollowingsocalledDevelopmentalSystemstheorists,Itaketheconceptofreproductionappropriateforevolutionarythinkingtoincludeevery-thingthatisrequiredforthereplicationoftheliecycle.Inthehumancasethismightinclude,forinstance,schoolsandhospitals.SeeS.Oyama,P.E.Griffiths,andR.D.Gray, Cycles of Contingency: Developmental Systems and Evolution, Cam-

bridge,Mass.:MITPress,2001.

to the longer term and greater changes to the environment changesconstituted most signicantly by the changing patterns o lie sur-rounding it.

Reductionism has, rom its beginnings, been greatly inspired by

our success in building machines, and even philosophers who haveabandoned the epistemological dream o reductionism, the explana-tion o everything in terms o physics, still oten adhere to versionso mechanism, the view that the unctioning o complex systems,including biological systems, should be understood by analogy withmachines.4 So it is worth refecting or a moment on how dierentthe workings o a machine are rom the hierarchy o processes thatI have just sketched. The parts o a machine are not unchanging, ocourse, but their changes constitute a relentless and one directionaltrend towards ailure. A good machine starts with all its parts pre-cisely constructed to interact together in the way t hat will generate itsintended unctions. The technical manual or my car species exactly

the ideal state o every single component. As riction, corrosion, andso on gradually transorm these components rom their ideal orms,the unctioning o t he car deteriorates. For a while these ailing com-ponents can be replaced with replicas, close to the ideal types speci-ed in the manual, but eventually too many parts will have deviatedtoo ar rom this ideal, and the car will be abandoned, crushed, andrecycled.

Reductionism is almost precisely true o a car. We know exactlywhat its constituents are they are listed in the manual and weknow how they interact: we designed them to interact that way.

SincedeliveringtheselecturesIhavehadoccasiontolookmorecloselyataninfluentialversionofmechanismthathasbeenpromotedrecentlybyanumberofphilosophers,especiallyinaseriesofrecentpapersbyCarlCraverandcollabo-rators.(SeeP.K.Machamer,L.DardenandC.F.Craver,ThinkingaboutMech-anisms, Philosophy of Science, 6: 1-25,2000;C.F.Craver,BeyondReduction:Mechanisms,MultifieldIntegration,andtheUnityofScience,Studiesin the His-tory and Philosophy of the Biological and Biomedical Sciences, 36:33-396,2005.)Thisexplicitlyanti-reductionistmechanismisgenerallyverycongenialtotheper-spectivedevelopedintheselectures.Thetermmechanismisusedtostresstheimportanceofdistinguishingasetofinteractingconstituentsthatmustbeunder-stoodatseveraldifferentstructurallevels.ItseemstomethatthedisanalogieswithmachinesthatI stressinthetextaresufficientlyimportanttomakethechoiceoftermunfortunate,thoughthisis,ofcourse,amatterofnomorethan

terminologicaltaste.


8/28

1


15

First Lecture

Refection on the dynamic and interacting hierarchy o processes thatconstitute lie should make us suspect that a very dierent picture isrequired.

An extreme reaction to this disanalogy might be that we should

question the very idea o dissecting lie processes into static things. Ishall not take such an extreme position. One reason I shall not is that,most strikingly in the last ew decades, mechanistic and even reduc-tionistic explanations have provided extraordinary insights into liv-ing processes. Indeed, our understanding o the molecular mecha-nisms underlying living processes has been growing at a rate thatperhaps exceeds any explosion o knowledge in the history o science.This growing understanding o the mechanical or quasi-mechanicalinteractions o molecules promises ever growing abilities to inter-vene in lie processes, or example in combating disease. Certainlythe processes o lie are highly dependent on these mechanisms. It iseven arguable that science is inescapably mechanistic; certainly its

most impressive and uncontested achievements have been based onmechanical models. But even i this is all true, the great dierencesbetween living things and machines should tell us something veryimportant about such scientic insights. Mechanical models, assum-ing xed machine-like ontologies, are at best an abstraction rom theconstantly dynamic nature o biological processes. And it is this per-vasive act about biological science that is central to explaining thephilosophical diculties in characterising the constituents o liethat biologists hypothesise. I, indeed, science is essentially a n exami-nation o mechanisms, this points to ultimate limits i n the ability oscience to understand lie. In the next lecture, however, I shall briefyconsider some scientic ventures which promise a more realisticapproach to biological processes.

Let me summarise the problem that I now want to address. Thereductionist believes that in the end there is nothing in the world butthe stu o which things are made let me call this basic physicalstu. O course, the reductionist does not s ay, bluntly and absurdly,that houses, or example, dont exist. The claim is rather that a houseis, ultimately, nothing but an aggregate o physical stu, and allthe properties o any house can, in principle, be ully explained byappeal to the properties and relations o basic physical stu. So thereis a possible, microphysically grounded, account o the world which

would have no need to mention houses. I am insisting, on the con-

trary, that there is a whole hierarchy o increasingly complex thingsthat really exist, and that have causal powers that are not reducibleto the mechanical combination o the powers o their constituents.Yet I have also claimed that the things we distinguish in our descrip-tions o lie, at least, are always to some extent abstractions rom the

dynamic processes that ultimately constitute lie. This second claimmay seem to undermine the reality o the members o the biologicalhierarchy to which the rst claim attributes causal powers. I mustnow try to show how these theses can be reconciled.

Let me start with a very brie and abstract answer, and then illus-trate what I mean with a homely example. The processes o lie are ocourse massively heterogeneous. This heterogeneity is expressed, orexample, when we inventory the thousands o chemical species to beound at any instant in a cell. Although such an inventory is a staticsnapshot o a dynamic entity at best an idealised description o thecell, thereore the molecules we distinguish are more or less tran-

sient oci o causal power, real nodes in the astonishingly complexcausal nexus that drives the cellular processes. Crucially, they are notmerely nodes in an upward fowing casual cascade rom the micro-physical, but equally in a downward fow o causal infuence romcomplex things to simpler things. Now the homely example, rom avery high level in the causal hierarchy.

Readers amiliar with South Central Amsterdam will be amiliarwith Albert Cuypstraat. This street has an unusual capacity to attractpeople, a capacity which, I suggest, has signicant similarities to theability o a fower to attract bees, or the ability o a magnet to attractiron lings: all are causal powers o individual things. The particularcausal power o Albert Cuypst raat will be obvious to anyone wander-ing around the streets in the immediate vicinity: while there will bea light scattering o people in these surrounding areas, immediatelyone reaches Albert Cuypstraat one will encounter a dense throng.The reason is no mystery, o course: this is a busy street market. Themarket could not exist without the people (and stalls, and products)that make it up, but equally there are properties o the market itselthat attract the people to it.

The powers o this market are exactly matched to the powers othe people it attracts. They must know it is market, or instance, and

how to get there. These are not dicult accomplishments: I mysel


9/28

16


1

First Lecture

managed to acquire them within a ew days o arr iving in Amsterdam.But o course I had acquired many o the necessary skills years ago:knowing what a market is, how to buy things, and so on. My returnto the market to orage ater my rst accidental encounter with it is,however, a more complicated achievement than, say, returning to aplace where I had previously discovered edible berries. I would not besimilarly drawn to return to a place where I had seen delicious look-ing ood through the window o a private house, or instance, andI would not return to the market at our oclock on Sunday morn-ing. The market is a social institution o a kind that I have learned tonegotiate reliably. By learning this I have also become willingly, Ishould add susceptible to the attractive casual powers o this insti-tution. The market depends or its existence on the people who gothere to buy and sell; but it is simultaneously the power o the mar-ket that attracts the people that constitute its continued existence.And, insignicant though these may seem, the market eects changesin the people it attracts it may determine, or example, what they

eat or dinner. This is the sort o thing that I mean by a node in thecausal nexus. I shal l suggest that this model, incorporating the devel-opment o t wo-way causal interaction between a complex thing a ndits constituents, is the r ight model or interactions at many dierentlevels o structural organisation.

There is no better example o the consequences o the shit rom astatic to a dynamic view o lie than the infuence o Charles Darwinsrevolutionary ideas on the subject o his most amous work, biologi-cal species. It may perhaps be thought that sorting organisms intospecies is more like constructing the automobile companys modelcatalogue than a part s list or one model. But, rst, a majority o phi-

losophers concerned with biology now hold that species should beseen as individual things, components o the evolutionary process.5And, second, sorting organisms into kinds raises many o the sameissues as sorting, say, molecules or parts o molecules into kinds:classication is an essential part o scientic activity at any level oorganisation. The classication o organisms is both the most widelydiscussed and the most ancient such project indeed a project thatsome believe was delegated to Adam when God invited him to name

5 ClassicstatementsofthisthesisareM.Ghiselin,ARadicalSolutiontotheSpe-cies Problem, Systematic Zoology 23: 536-5,19.D.L. Hull, Are Species

ReallyIndividuals?Systematic Zoology25:1-191,196.

the animals. One crucial point that will emerge rom considerationo this topic, and which should be less surprising viewed in the lighto the general problem o abstracting objects rom processes, is thatthere is no uniquely correct way o classiying organisms: dierentinvestigative interests dictate dierent and oten cross-cutting modeso classication.6

There is an ancient philosophical tradition that u nderstands clas-sication as involving the identication o the essence o things oa kind: the essence is a necessary and sucient condition o beinga thing o that kind and also the eature that most undamentallyexplains the properties characteristic o that kind. So, or instance, acertain atomic structure might be both necessary and sucient or apiece o stu to be iron and, at the same time, provides an explana-tion o why that stu has properties being magnetic, being easilyoxidisable, and so on characteristic o iron. Whether or not such anidea works or chemistry, one thing that a lmost everyone now agrees

on is that nothing similar works or biology.7 A sucient explanationo this ailure is the agreement that one biological kind can evolvegradually into another. The identication o a kind o organismexisting at this moment is an abstraction rom a continuous processlinking these current organisms through time to a long series o verydierent organisms and, indeed, i we trace evolutionary history backto a common ancestor and thence orward to the present, connect-ing any two currently existing k inds o organism. There is no way ounderstanding this link as consisting o a denite number o distincttypes, each dened by its u nique essence.

Just as evolutionary theory has put an end to certain traditional

ideas about biological classication, so it underlies more contem-porary views. What most contemporary theorists agree is that bio-logical classication should refect the evolutionary relationships

6 Forfurtherexplanationofthisview,seeDupr,Humans and Other Animals,chs.1and2.

AclassicargumentofthiskindisD.L.Hull,TheEffectofEssentialismonTaxon-omy:2000YearsofStasis,BritishJournalforthePhilosophyofScience15:31-326;16:1-18,1965.Anumberofrecentcommentatorshavesuggestedthattheessentialismattributedtopre-Darwinianthinkersbyrecentanti-essentialistsissomethingofacaricature,butthisofcourseonlystrengthenstheanti-essential-istposition.See,e.g.,M.P.Winsor,Non-essentialistmethodsinpre-Darwinian

taxonomy,.Biology and Philosophy18:38-00,2003.


10/28

18


19

First Lecture

between dierent kinds o organisms. Evolutionary history has tra-ditionally been represented as a tree, with branches representingevolutionary divergences and the smallest twigs representing themost nely distinguished kinds, species. For a while the dominantview, the so-called Biological Species Concept especially associatedwith one o the twentieth centurys most infuential evolutionists,Ernst Mayr, refected a theory about the mechanism o evolution-ary divergence.8 The separation o branches o the tree, it was sup-posed, required that organisms on dierent branches be reproduc-tively, and hence genetically, separated rom those on other branches.Thus species were thought o as a reproductively connected group oorganisms, reproductively isolated rom all other groups. Unortu-nately this idea oten ts poorly with biologists sense o what consti-tutes a species. Many groups o what seem to be well dened speciesin act show continuous reproductive links and, on the other hand,what seem like homogeneous species oten divide into separate popu-lations with little or no reproductive connection between them. In

addition there is a major problem with asexual species, the memberso which appear to be reproductively isolated rom everything excepttheir direct descendants and a ncestors.

Since the 1960s an alternative programme has advocated a moredirect relationship between the evolutionary tree and biological clas-sication. So-called cladistic classication, or cladism, a version othis idea and increasingly the dominant school among taxonomists,aims directly to identiy the branching points in the evolutionarytree.9 Ideally, a distinct name would be given to any set o organ-isms lying between two branching points on the tree. The terminalbranches will be the species. Because the patterns o branching in

dierent parts o the tree ca n be very diverse, this oten ai ls to refectprior notions about how many species there are and how dierent

8 See,e.g.E.Mayr,Animal Species and Evolution, Cambridge,Mass.:HarvardUniver-sityPress,1963.

9 The locus classicus forthis idea isWilliHennig, (1966).Phylogenetic systematics.Urbana:UniversityofIllinoisPress.Cladismisgenerallyunderstoodasaformofphylogeneticclassificationthatinsiststhatallgroupsbymonophyletic,whichistosaythattheymustincludeallandonlythedescendantsofanancestralspecies.Lessrigorousversionsofphylogeneticclassification,sometimesreferredtoasevolutionarytaxonomy,relaxthisrequirementsothatitispossibletodenysuchapparentlyparadoxicalclaimsas,forinstance,thatbirdsareakindofdinosaur.Theargumentsbelowapplytobothversionsofphylogeneticclassification.

they are rom one another. But, cladists have tended to conclude, somuch the worse or our existing notions about species.10

Beore continuing with the discussion o classication, I mustnow introduce a topic that will be important throughout these lec-tures. There is an English expression, the elephant in the room. Theelephant reers to a problem which, as is the way with elephants, isextremely obvious, but which, or whatever reason, all participantsin a discussion decide to ignore. There is an elephant in the room obiological classication indeed it is an elephant that can be oundin many areas o biology and which I shall r udely point out at severalpoints in these lectures. So let me now describe this elephant.

This elephant is not one large object, but a huge number o verysmall ones, the microbes. Microbes have been the only kinds oorganisms on this planet or the majority, perhaps 80%, o the his-tory o lie. And they continue to be the dominant lie-orm. It is cal-

culated that even by sheer biomass microbes continue to constituteover hal o contemporary terrestrial lie. And the most extreme ter-restrial environments remain too hot, cold, dark, or chemically hos-tile or other lie-orms.

I should explain what I mean by a microbe. For now I shall thinko microbes as including all single-celled organisms though I shallsuggest later that this concept is not unproblematic. Two o the threebranches o what is generally considered to be the most undamentaldivision among organisms consist o microbes. These are the Super-kingdoms, or domains, Bacteria and Archaea. The third domain, theEukarya, is a lso mostly composed o microbes, so-called protists, but

also includes multi-cellular organisms, animals, plants and someungi. To emphasise their almost c ameo role against the backdrop omicrobial lie, I and my collaborator on this topic Maureen OMalleyare attempting to popularise the word macrobe to reer to thoseorganisms, such as ourselves, that are not microbes. It seems absurdthat we should have a word or the great majority o lie orms, butnone or the small mi nority that this word excludes.11

10 Avarietyofphilosophicaldiscussionofthemainpositionsonthenatureofspe-ciescanbefoundinM.Ereshefsky,The Units of Evolution: Essays on the Nature ofSpecies, Cambridge,Mass.:MITPress,1991;andR.A.Wilson,Species: New Inter-disciplinary Essays, Cambridge,Mass.:MITPress,1999.

11 Forthisproposalandmoredetailed elaborationof most ofthepointsabout


11/28

20


21

First Lecture

I should now explain the relevance o this elephant to classica-tion. Both the Biological Species Concept and cladistics have di cul-ties with asexual reproduction. The problem has already been notedor the Biological Species Concept. Cladistics is threatened in a some-what dierent way. To see this we need to look more careully at whatis meant by asexuality. Sexuality is normally t hought o, biologically,as a device t hrough which two parents contribute genetic material inthe production o a new individual. Asexuality, by contrast to this,is oten thought o as parthenogenesis, the production o ospringby a single parent. Sexual organisms sometimes abandon sexualityin avour o the latter method o reproduction, sometimes use it asan optional alternative. But even more than a device or acilitat-ing genetic collaboration, sexual reproduction is part o a system orrestricting the fow o genetic material. As the Biological Species Con-cept, with its emphasis on reproductive isolation makes clear, sexualmacrobes go to great trouble to make sure that their gene exchangetakes place with very similar organisms. Indeed one infuential

descendant o the biological species concept is called the mate-rec-ognition concept, recognising the diversity o mechanisms by whichorganisms, macrobes anyhow, ensure that they nd the right part-ners or genetic collaboration.12 The asexuality typical o microbes13should be seen by contrast to this aspect o sexuality. As has becomeincreasingly clear over the last several decades, rom the perspectiveo genetic exchange, microbes are not so much asexual, as massivelypromiscuous. Microbes have a number o dierent mechanisms orexchanging genetic material, and they use them ully. They havemechanisms or so-called conjugation, exchanging genetic materialsin a way analogous to macrobe sexuality; DNA is transerred romone organism to another by phages, viruses specic to microbes; and

microbesmadehereandlaterintheselectures,seeM.OMalleyandJ.Dupr,SizeDoesntMatter:TowardsaPhilosophyofMicrobiology,Biology and Philoso-phy, forthcoming2006;andJ.DuprandM.OMalley,MetagenomicsandBio-logicalOntology,Studies in the History and Philosophy of Biological and BiomedicalSciences, forthcoming200.

12 SeeH.E.H. Paterson,TheRecognitionConceptofSpecies,inSpecies and Spe-ciation, edE. Vrba. Transvaal MuseumMonographNo. .Pretoria: TransvaalMuseum.

13 Inthisandthefollowingparagr aph,myreferencestomicrobesapplymainlytothesimplerorganisms,theBacteriaandArchaea,lackingnuclearmembranes,whicharegenerallyreferredtoasProkaryotes.MattersaresomewhatmorecomplexanddiverseformicrobialEukaryotes(protists).Iusethetermmicrobesinceit

ismuchmorefamiliar,andnoseriousconfusionislikelytobeengendered.

many microbes can pick up ree, or naked, DNA rom the environ-ment. These mechanisms can acilitate DNA exchange between dis-tantly related orms, even across the three domains at the base o bio-logical classication. Because o the prevalence o these processes,typical microbes will include genetic material rom numerous dis-tinct lineages.

The problem with the phylogeny o microbes, then, and one reasonthat ew i any microbial taxonomists endorse cladism, is that there isno unambiguous evolutionary tree on which to superimpose a ta xo-nomic system: microbes have too many diverse ancestors.14 Or, at anyrate, they do i any past organism rom which they derived geneticmaterial is counted as an ancestor. Microbes or a long time seemedpractically almost impossible to classiy simply because o theirdimensions. The development o tools capable o providing detailedinspection o genomes oered a solution to this problem. Compari-son o microbial genomes would allow biologists to track the phlyo-

genetic histories o particular bits o microbial genome sequence, andiner the phylogeny, the evolutionary history, o microbes. In the earlydays o genomic classication o microbes a set o ribosomal geneswas identied as part icularly suitable or this purpose, and these con-tinue to this day to provide an important resource or classicatorywork. However, it is also becoming clear that the phylogenetic historyproduced using these genes is to an important extent an arteact othat choice. Using dierent genomic criteria the same organisms canappear in very dierent parts o the phylogenetic tree. This shouldbe no surprise. What it indicates is merely that the genetic relationsbetween microbes do not really orm a unique tree at all, but rathera web. It may be useul or particular purposes to represent the evo-

lutionary relations between microbes in the orm o a tree, but wemust remember that this is an abstraction rom a much more com-plex reality.

1 Thisremainsa controversialmatter amongmicrobiologists.A strongadvocateoftheimpossibilityofdefiningamicrobialphylogenyisFordDoolittle(seee.g.,W.F.Doolittle,PhylogeneticClassificationandtheUniversalTree,Science28,212-28,1999.).AninfluentialresisterisCarlWoese,thescientistresponsiblefordistinguishing betweenthemicrobialsuperkingdomsArchaeaand Bacteria

mentionedabove.Aswillbeclear,Ifindtheformerargumentcompelling.


12/28

22


23

First Lecture

I do not, in act, believe that there is a uniquely correct way o clas-siying even macrobes,15 but the case is even clearer or microbes.16The ailure o evolution to provide us with a unique and unequivo-cal method o biological classication enables us to see that thereare many real discontinuities across the vast spectrum o dierentorganic orms. And dierent discontinuities can ground dierentways o classiying these, suited to di erent purposes, again both sci-entic and mundane. Certainly we can imagine t hat God, had he cre-ated the plants and animals, would have known how many distinctkinds he had come up with. Phylogenetic classication can be seenas a device that might have reconciled this a ncient doctrine, to somedegree, with post-Darwinian biology. But it cannot do that job. Itmay be an irreplaceable approach to biological classication, but it isnot the only one possible, and it is an abstraction rom the real com-plexity o biological relations. Once it is clear that only under quitespecial circumstances does evolution determine a unique way o clas-siying organisms, we should reject the cladists indierence to the

convergence o evolutionary theory on existing categories. Classica-tions serving dierent biological interests ecology rather than evo-lution, or instance and even more practical interests such as thoseo the orester, the herbalist, or the che may equally be grounded indistinct natural discontinuities.

To mention one practical issue that is easily misunderstood byailing to understand this point, we might consider the problems obiological conservation. One might imagine that the aim o conser-vation is to save as many species as possible. Though I dont claim toknow what the goal should be Id guess that it would be a mixtureo aesthetic, utilitarian, ethical, and probably other aspects the sim-

ple idea just mentioned surely wont do. Most undamentally this isbecause it is incoherent: there is no unique way o counting the spe-cies. But even ignoring this, rom any sensible conservation perspec-tive not all species are equal. Apart rom quite legitimate aestheticarguments that the loss o tigers or gorillas would be more seriousthan the loss o one member o a large group o beetles, the ormerare plausibly ar more biologically distinctive than the latter. Thereis, at a ny rate, no absolute conception o the species that contradicts

15 SeemyHumans and Other Animals, op.cit.,chs.3and.16 This argument is spelledout in greaterdetail inOMalleyand Dupr, Size

DoesntMatterop.cit.

this idea. Conservation o microbial diversity is an issue, and poten-tially a very important one, that has hardly been considered per-haps because the actual objectives o conservationists typically arepredominantly aesthetic.

Does the denial that species represent a unique division o bio-logical reality mean that they are unreal, or play no part in biologicalexplanation? I have mentioned the widely held view among philoso-phers o biology that species are not kinds at al l, but individuals. Thisview is lin ked to the idea that species are branches o the evolutionarytree and thereore inherits the limitations o that idea. However to theextent that the evolutionary tree has branches at all it is sometimesuseul to think o species as spatio-temporally extended individualsthat can be identied with these branches. It is useul or theorisingmuch o macrobial evolution, and macrobial species should oten betreated as individual things with signicant causal powers. But mac-robial species can be treated as individuals, because they do things:

or example, they speciate, divide into two distinct species. Processeso macrobial speciation, the emergence o new biological orms, areoten very real, a nd important or understanding biological diversity.Contrary to one popular idea, speciation is not always a slow or grad-ual process. About hal o the species o fowering plants, or instance,appear to have arisen by a process o polyploidy, the doubling in sizeo the genome.17 Such a process creates instantaneous inertility withthe ancestral species, and may produce immediate changes in thephenotype. Sometimes this is t he doubling o the genome o a singleparental organism, sometimes it happens through the hybridisationo two related plants. Because many plants are sel-ertile, the appear-ance o a single polyploid individual may, i circumstances are propi-

tious, ound an entire new species.

The preceding case provides a nice reductive explanation o organ-ismic diversity in terms o molecular processes. But species also playa part in explanations at their own level, and can be a ected by theirinvolvement in processes that could be thought o as at a higher level.Species interact with one another as, or instance when the mem-bers o one prey on or parasite the members o another. This com-plex interaction will help to determine the dynamics o the size o the

1 SeeK.L .Adamsand J.F.Wendel,PolyploidyandGenomeEvolutionin Plants,

Current Opinion in Plant Biology8:135-11,2005.


13/28

2


25

First Lecture

participant species. In the longer term, interactions between preda-tor and prey species will direct the evolution o each as is well doc-umented in the phenomenon reerred to, in an unortunately com-mon militaristic vein as an evolutionary arms race. The lineageso cheetahs and gazelles, or instance, exhibit ever greater speeds astheir lives depend on capturing or escaping one another. These maybe interpreted as examples o large complex things species inter-acting with one another, but their signicance does not depend onthis interpretation. The more general point is that classiying a thingas a cheetah identies a set o processes in which it can be involved.Classiying it in other ways might identiy dierent processes. Suchpossibilities o multiple, perhaps cross-cutting, classication becomemore salient as classication becomes less determinate. This will bemost clearly the case a mong the microbes.

Particular characteristics o human societies have also aectedbiodiversity in ways that are best described by identiying species,

indicating a very dierent kind o interaction in which species (ormerely organisms by virtue o being members o a species) may beinvolved. It may be that i tigers go extinct it is in part due to thebelie, among signicant proportions o the human species, thatconsuming tiger penises has great medical benets. However deci-sive this actor may or may not be, it is certainly entirely possible orquite specic human belies to aect the trajectory o a non-humanspecies, and there are surely many real instances o this happening.Belies about the relative desirability o rainorests and marketabletimber are exterminating species as I write. The practice o selectivebreeding, now oten involving targeted intervention at the molecularlevel, provides another obvious set o examples.

I want now to turn to a quite dierent biological concept, the con-cept o a gene, and again want to demonstrate the lack o any uniquemotivation underlying this concept, and the consequently distinctkinds o object that may serve these diverse concerns. Historically,the concept o a gene was introduced in the context o the experi-ments on breeding in the early twentieth century, deriving rom therediscovery in 1900 o Mendels work. The gene was a hypotheticalobject that explained the distinctive patterns o inheritance o ea-tures o organisms discovered by Mendel. It was thus conceived asthe transmittable cause o a specic phenotypic di erence. For some

time it remained a matter o debate whether genes should be thought

o as material things at all, or rather conceived instrumentally asmere calculating devices. But by the time o the unravelling o thestructure o DNA in 1953, it had become widely agreed that geneswere material things and that they were located on chromosomes.This classical or Mendelian concept the underlying cause o a di-erence remains in u se today, particularly in medical genetics, butas knowledge in molecular genetics has expanded exponentially inthe last hal century it has actually become more dicult to relatethe classical gene to any particular molecular entity.18

Consider, or instance, the cystic brosis gene. This i s a recessivegene, meaning that to suer its eect, the severe congenital diseasecystic brosis, one must receive the gene rom both parents. The genepretty accurately obeys Mendelian patterns o inheritance. But whatis it? That is a harder question. Cystic brosis results rom the ailureo the body to make a particular protein, cystic brosis transmem-brane conductance regulator, involved in the production o channels

that conduct salt through certain membranes. The cause o this ail-ure is a deect (in both copies) o a bit o DNA sequence called theCFTR gene. However, there are more than a thousand known deectsin this sequence that produce cystic brosis, though producing vari-ably severe symptoms. So the Cystic Fibrosis gene is actually a largeset o variations in a bit o DNA sequence. A set o variations is atleast an unusual kind o object.

The gene CFTR, on the other hand, is a rather dierent kind othing. It is generally dened as a sequence o 188,698 base pairs onthe long arm o human chromosome 7. This sounds a much morematerial kind o thing. However, it should be noted that there is no

exact sequence o base pairs necessary to constitute a unctioningCFTR gene. The genetic code, as is well known, is redundant, so thatmany changes will have no eect at all on the unctioning o the gene,and there are very likely to be changes that do make a dierence tothe transcription o the gene, but do not prevent its proper unction-ing. In short, then, the CFTR is a denite stretch o DNA sequence,though one that allows a good deal o variation; the cystic brosis

18 ProblemswiththeconceptofagenearediscussedbyLennyMoss,What GenesCant Do,Cambridge,Mass.:MITPress,2003,andin theessaysinP.Beurton,R.Falk,andH.-J.Rheinberger(eds.),The Concept of the Gene in Develoment andEvolution, Cambridge:CambridgeUniversityPress,2000.


14/28

26


2

First Lecture

gene is any o a large set o dysunctional variations in the same parto the genome or, perhaps, as we shall see, in quite dierent partso the genome.

The CFTR gene, at any rate, looks a good deal more like the sorto thing people expect a gene to be in the age o genomic sequenc-ing: a specic par t o the genome with a specic molecular unct ion.However, as so oten in biology, things are not as simple as they mayseem when we try to generalise this concept o the gene. A hint o thetrouble can be seen in the act that the number o genes in the ullysequenced human genome is currently esti mated as being somewherein the range o 20,000-25,000. It is oten noted that this is a muchsmaller number than had been assumed necessary or the estimatednumber o gene-related human traits. But a more important puzzleor the moment is the vagueness o this estimate. Why, one may won-der, can they not just count them? The complexities that stand in t heway o this task can only be sketched in the brieest way, but even such

a sketch will be su cient to make my overall philosophical point.

Properly molecular genes are oten thought o as a part o thegenome that codes or a particular protein. However, as a denitionthis raises numerous problems. Typically genes (in macrobes, at anyrate) are composed o alternating sequences called exons and int rons.Ater the gene is transcribed, into RNA, the introns are edited out,and the exons are then translated into protein molecules.19 How-ever, in many, perhaps most, cases there are alternative ways o splic-ing the exons into nished RNA sequence, and some bits may be letout. Further changes may be made either to the RNA sequence or tothe subsequently produced proteins. In some cases elements o other

genes may be incorporated. Thus the relation between moleculargenes and proteins is not one to one, but many to many. Some genesare involved in making hundreds o distinct proteins.

It still might seem that the genes could be counted, even i theywere then ound to have much more diverse unctions than mightonce have been supposed. But things get worse. First, genes can over-lap. So a certain sequence can be part o two quite distinct primary

19 Thereismuchtobesaid,andagooddealthathasbeensaid,aboutallthesesemanticmetaphorsediting,transcribing,translating,codingbutthatisnotatopicIshalladdresshere.

RNA transcripts w ith quite dierent subsequent histories. Worse still,DNA is not always read in the same direct ion. So a sequence may bepart o one gene read in the normal so-called sense direction, butpart o another when read in the opposite anti-sense direction. Phi-losophers Paul Griths and Karola Stotz have investigated empiri-cally how many genes biologists claim to see in problematic bits osequence and the answer, perhaps unsurprisingly, is that dierentbiologists see dierent numbers o genes.20 It would perhaps be pos-sible to regiment the concept suciently so that the answer to suchquestions could be decided mechanically, but this would only con-ceal the real philosophical problem: Nature has declined to dividethe genome into a unique set o constituent entities. Dierent, over-lapping, and non-contiguous elements o the genome are involved indierent biological unctions. A realistic conclusion is that a molecu-lar gene is any part o a genome that a biologist has some reason totalk about. (Just as, indeed, it is sometimes said that a species is anygroup o organisms a competent taxonomist decides to put a name

to.)

In act this discussion has only scratched the surace o the diver-sity o entities that may legitimately be reerred to as genes. The pro-tein coding genes that I have been discussing make up only a ewpercent o the DNA in many macrobial genomes, including our own.Until quite recently it used to be said that the remaining large major-ity o the genome was junk, a testament to the pernicious activity ogenetic parasites.21 It is becoming increasingly clear that much othis so-called junk serves important biological unct ions. At the veryleast it is essential or structural eatures o the genome. But it alsoappears that many parts o it are tra nscribed into RNA and that these

RNA molecules play important roles in the unctioning o the cell. It

20 K.Stotz,P.E.Griffiths,etal.,Howscientistsconceptualisegenes:Anempiricalstudy.Studies in History & Philosophy of Biological and Biomedical Sciences, 35:6-63,200.

21 Thesewere,andstillsometimesare,thoughtofasthetrulyselfishgenesmerelycompetingwithoneanothertooccupyspaceinthegenome.Thetransposableelements,thediscoveryofwhicheventuallywonBarbaraMcClintocktheNobelPrize,comeclosesttorealisingthisimage,apparentlyconcernedonlywithmak-ingmorecopiesofthemselvesinthegenomeandoftenconstitutingalargepro-portionofthegenome.Eventhese,however,areincreasinglysuspectedofserv-ingsome more altruistic purposeof contributing something to the widerorganism.


15/28

28


29

First Lecture

has also been know or a long time that non-coding sequences in thegenome serve to regulate the expression o protein coding sequences,and a growing number o di erent kinds o such regulatory sequenceare now distinguished. So, in short, there are many very dierentkinds o sequence that molecular biologists have reason to distin-guish, and hence many dierent kinds o genes.

Nature, then, no more determines how to divide the genome intogenes, than she does organisms into species. Particular parts o thegenome can, however, as in the other examples I have considered, pro-vide nodes on the causal nexus that are appropriate points o ocusor particular investigative purposes. Reductionist explanation o thepower o genes is amiliar enough. Indeed, it was in large part thechemical explanation o the stability, complexity, and replicability othe DNA molecule that made the description o its structure such anextraordinary scientic achievement. A moment ago I pointed to themuch more specic way in which various genetic anomalies help to

explain a disease such as cyst ic brosis. Less amiliar is the extent towhich the DNA in a cell is in constant two-way interaction with otherconstituents o the cell. What was or a long term known (approv-ingly) as the Central Dogma o molecular biology was the view thatinormation fowed in one direction only, rom DNA to RNA to pro-tein. In accordance with this dogma it was supposed that the unctiono RNA was primarily to carry inormation rom DNA to proteins.But today the study o the vast number o dierent RNA moleculesand their infuence on gene expression is one o the most rapidlydeveloping elds in molecular biology. One class o these molecules,the so-called RNAis, which can block the expression o a codinggene, are currently considered one o the most exciting prospects or

molecular medicine. Many proteins, too, interact with nuclear DNAand aect the transcription o particular sequences.

It is still o ten supposed that the genome is the ultimate director othe process by which a n organism develops, a supposition expressedin metaphors such as blueprints, recipes or programmes. This is , inact, an expression o the reductionist philosophy that I reject. Forreductionism, a complex process such as organismal developmentcan only be explained by causal infuences rom smaller constituents.DNA is seen as the largely unchanging structure that mediates thistranser o casual power rom below. The vision o DNA as a nodethrough which causal infuence passes both upwards and downwards

o course contradicts this picture, but does so on the basis o increas-ingly undeniable scientic evidence. Genes, in the end, are the diverse,nested, and overlapping sites in the genome where these casual infu-ences are ocused, at dierent times, in dierent ways, and oten indierent ways at the same place.

A good way to get a sense o the implications o this picture is tocontrast it with the reductionist picture o genetics that has groundedan extremely infuential view o evolution but one that must now beseen as highly simplistic. I the genome were indeed an unchangingrepository o inormation, then rom the perspective o evolution-ary theory one could see evolution as simply a temporal sequence ogenomes. The organisms or which they were described as the blue-prints, or the recipes, would develop as the genome dictated, andtake their chances in the lottery o lie, and the best ones would beselected. But all they would pass on to the next generation were themost successul blueprints. Those amiliar with the writings o Rich-

ard Dawkins should recognise this picture. Only the selsh genes intheir immortal coils live on through evolutionary time.22

This picture should already look suspect when one sees that DNAis only one, admittedly very important, component o an interact-ing system o molecules, and that the whole system is passed on tothe ospring in the cytoplasm o the maternal egg. But it now turnsout that changes to the DNA itsel that occur during the lie o anorganism can be transmitted to ospring. The best studied o suchprocesses is methylation, a chemical modication o the DNA thatprevents the expression o particular gene sequences. This is mostamiliar in stories about imprinting, the dierential methylation o

paternal and maternal DNA, claimed to refect competing male andemale evolutionary interests. But it is by no means restricted to this.

22 SeeRichardDawkins,The Selfish Gene,Oxford:OxfordUniversityPress,196,andmanysubsequentbooks.Thereisagooddealofmuchmoresophisticatedtheoreticalworkonevolutioncurrentlyunderway,thoughnoneunfortunately,thatthreatenstocompetewithDawkinsssalesvolumes.ParticularlyimportantrecentcontributionsincludeM.J.West-Eberhard,Developmental Plasticity and Evo-lution, NewYork:OxfordUniversityPress,2003;andEvaJablonkaandM.J.Lamb,Evolution in Four Dimensions: Genetic, Epigenetic, Behavioral, and Symbolic Variation inthe History of Life, Cambridge,Mass.:MITPress,2005.Recentinsightsthathaveunderminedthesimplistic,gene-centredpictureofevolutionarenot,ofcourse,limitedtothosebrieflymentionedinthepresenttext.


16/28

30


31

First Lecture

One amous case is a study o the eects o maternal care on rats.Absence o such care, especially o licking by the mother, producednervous, earul ospring and, unexpectedly, these characteristicsappear to be passed on to the ospring o the neglected animals.23 Ithas been veried that maternal care produces methylation o genesin the hippocampus, though the mechanism by which this changeis passed on to subsequent generations remains obscure. There isalso a amous, though also still controversial case in recent humanhistory, the Dutch amine o 1944-5. Unsurprisingly, mothers whoexperienced this amine tended to have small babies. Much more sur-prisingly, their generally well-ed children also tended to have smallbabies. Many have concluded that transmitted methylation patternsinduced by the shock o malnutrition explain this phenomenon. 24Students o such phenomena are even beginning to call themselvesneo-Lamarckians, transgressing perhaps the most inviolable tabooo twentieth century biology.25 The so-called epigenome, the set oinherited mechanisms that determine how genes are expressed, is

another booming area o research. One o the successor projects tothe Human Genome Project is the Human Epigenome Project, thataims to map the methylation sites on the human genome. Epigenom-ics more generally, the study o the interactions between the cellularenvironment and the genome, is poised to become an even more sig-nicant signicant eld o research than genomics itsel.

The picture I have tried to sketch will not please those who arewedded to the crystalline clarity that the mechanistic vision o lieoers. Shiting levels o organisation with shi ting, metamorphosingand even indeterminate constituents may seem like unlikely materi-als or understanding the exquisitely ordered and robust phenomena

o lie. And causal processes running upwards to exploit the diverseand specic capacities o countless chemicals and structures anddownwards to provide externally enorced constraints on the actions

23 F.A.Champagne,I.C.Weaver,J.Diorio,S.Dymov,M.Szyf,M.J.Meaney,Mater-nal CareAssociated withMethylationof the EstrogenReceptor-Alpha1bPro-moterandEstrogenReceptor-AlphaExpressionintheMedialPreopticAreaofFemaleOffspring,Endocrinology, 1:2909-15,2006.

2 See,e.g.,G.Vines,HiddenInheritance,New Scientist, 2162:2-30,1998.25 E.g.,E.JablonkaandM.Lamb,Epigenetic Inheritance and Evolution: The Lamarckian

Dimension,NewYork:OxfordUniversityPress,1995.

o those structures and chemicals, may seem to be hopelessly intrac-table objects o real insight and understanding.26

Yet it is also worth considering how inadequate the mechanisticparadigm is or understanding these phenomena. As I explained withthe example o a car, deterioration and ailure are the inevitable his-tory o a machine. Organisms, while perhaps all die i n the end, showno such inevitable tendency. Some live or millennia with no obvi-ous deterioration o vital unctions, and it is now a matter o livelydebate whether human aging is an inevitable process o deterioration,or rather a biological unction that we might, i we chose, nd wayso subverting. There are powerul reasons or thinking that eman-cipation rom the mechanistic paradigm is a precondition or trueinsight into the nature o biological processes.

I am not, o course, the rst person who has oered more complexand dynamic visions o lie than are possible within the constraints

o mechanism, and I shall end this chapter with one such vision thatexpresses, with a poetic elegance to which I can only aspire, a viewremarkably congruent with much o what I have said today. Thewords are rom Walter Pater, the British aesthete and philosopher,written in his Conclusion to the Renaissance, in 1893:

What is the whole physical lie but a combination o natu-ral elements to which science gives their names? But those ele-ments are present not in the human body alone: we detectthem in places most remote rom it. Our physical lie is a per-petual motion o them the passage o the blood, the waste andrepairing o the lenses o the eye, the modication o the tis-

sues o the brain under every ray o light and sound processeswhich science reduces to simpler and more elementary orces.

26 CarlCraverandWilliamBechtel,leadingproponentsofthecontemporarymech-anismmentionedinnote3,above,rejecttopdowncausationbutequally,andforsimilarreasons,denybottom-upcausation.Theyconsidercausation,strictusensu,tobeaconceptonlyapplicablewithinonestructurallevel.Bothtop-downandbottomupcausationtheyprefertodescribeasmechanisticallymediatedeffects.Again, Isuspect oursubstantiveviewsarequitesimilar,thoughI aminclinedtoamuchmorecatholicconceptionofcausality,andamsomewhatscep-ticalofanysharpdividebetweensameanddifferentlevels.(CarlF.CraverandWilliamBechtel,Top-DownCausationwithoutTop-DownCauses,Biology andPhilosophy,forthcoming2006.)


17/28

32


Like the elements o which we are composed, the action o theseorces extends beyond us: it rusts iron and ripens corn. Far outon every side o us those elements are broadcast, dr iven in manycurrents; and birth and (gestation) and death and the springingo violets rom the grave are but a ew out o ten thousand resul-tant combinations. That clear, perpetual outline o ace and limb

is but an image o ours, under which we group them a designin a web, the actual threads o which pass out beyond it. Thisat least o fame-like our lie has, that it is but the concurrence,renewed rom moment to moment, o orces parting sooner orlater on their ways It is with this movement, with the passageand dissolution o impressions, images, sensation, that analysisleaves o that continual vanishing away, that strange, perpet-ual weaving and unweaving o ourselves.

Spinoza Lecture ii

The

ConsTiTuenTs

of Life


18/28

35

second Lecture

In the previous chapter I tried to explain some o the dicultiesin dening central concepts in biology, and also oered a generalhypothesis as to why these diculties arise. The general hypothesis isthat many o these dicu lties stem rom the confict between on theone hand, lie itsel as a hierarchy o dynamic and constantly chang-ing processes and, on the other hand, our scientic understanding

as grounded on a picture o mechanistic interactions between xedand statically dened components. While not wishing to deny theextraordinary insight that mechanistic models have provided intolie processes, I tried to explain the deep dierences between livingsystems and the machines that have been such a central source oinspiration or science generally. Mechanistic models have given usextensive knowledge o many o the elements o which living systemsare composed, but they are i nadequate to provide a u ll picture o lieas a dynamic system.

Key concepts in biology, I suggested, are static abstractions rom

lie processes, and dierent abstractions provide dierent perspec-tives on these processes. This is a undamental reason why these con-cepts stubbornly resist unitary denitions. They speciy, more orless, the level at which we are abstracting, but nature does not deter-mine or us a unique mode o abstraction. This problem is centralto explaining the philosophical diculties that have been ound inattempts to provide unique denitions o two central categories inbiology, the species and the gene, diculties which I summarisedin the last chapter. While arguing that there is no unique and privi-leged way o dividing biological reality with these terms, I claimednevertheless that there were many and diverse real biological enti-ties alling under these concepts. In the most important cases, this

reality consists in the more or less transitory ocus that such entities,or example the particular parts o genomes sometimes identied asgenes, provide or causal processes. But these entities must be under-stood not only as inheriting causal powers rom their structural com-ponents, but also as recipients o causal infuence rom the largerentities o which they are part. This two-way fow o causal infuencethrough a shiting a nd diverse array o entities presents a very dier-ent picture o lie rom the pristine mechanism which still infuencesso much scientic thinking. In the second part o this chapter I shallsay something about how we might conceive the prospects or scien-tic progress when conronted with such a picture.


19/28

36


3

second Lecture

In the rst part o the chapter, however, I shall enrich the gen-eral view being developed by looking at some crucial levels betweenthe extremes o species and gene so ar discussed. I shall begin withprobably the most generally amiliar kind o biological entity, theindividual organism.

At rst sight it w ill seem quite obvious that I, or my cat, or GeorgeW. Bush, are discrete biological entities whatever else is. To adapt USSupreme Court Justice Potter Stewarts amous remark about por-nography, I know one when I see one. But when we consider a littlemore closely what is to be included in these entities, matters becomeless clear. A natural way o describing the limits o the individual,John Dupr, would be to imagine the surace that includes all theparts that move together when John Dupr moves, and treat all thematerial included within that surace as part o John Dupr. This isa good legal denition: i someone violates that space, or examplewith a shar p instrument, they a re considered grossly to have violated

my rights.

In the previous chapter I introduced an elephant in theroom the microbes, the overwhelming majority o living things.The elephant is still very much in the part o the room I am nowdescribing. Within the surace I just mentioned, my own, 90% o thecells are actually microbes. Most o these inhabit the gastro-intesti-nal tract, though within that, and elsewhere in the body, are a widevariety o niches colonised by microbial communities. Because o thediversity o these microbial ellow travellers, as many as 99% o thegenes within my external surace are actually bacterial.27

We are sometimes told that the human body should actually beconsidered as a tube, so that the inside o my mouth or gut shouldrather be considered as part o the outside surace o my body. Thiswill cer tainly reduce the microbial load in our own sel-images, but itis somewhat counterintuitive. Considering the legal perspective justmentioned, it would be a very implausible deence against charges ovarious orms o serious sexual assault, or example. And it is bio-logically questionable. I we examine t he inside surace o the gut wewill discover complex and ordered communities o bacteria w ithout

2 J.Xu,J.I.Gordon,HonorThySymbionts,Proceedings of the National Academy of

Sciences 100:1052-1059,2003.

which the interace between ourselves and the things we eat would beseriously dysunctional. Our sy mbiotic microbes are essential to ourwell-being. Particularly interesting is the growing understanding thatsymbiotic bacteria are required or our proper development. It wasrecently reported, or example, that environmentally acquired d iges-tive tract bacteria in zebrash regulate the expression o 212 genes.28

In act, or the majority o mammalian organism systems that inter-act with the external world the integumentary (roughly speaking,the skin), respiratory, excretory, reproductive, immune, endocrine,and circulatory systems, there is strong evidence or the coevolu-tion o microbial consortia in varying levels o unctional associa-tion.29 For these reasons, some biologists are now proposing a secondhuman genome project the human biome project that will cata-logue all the genetic material associated with the human, includingthat o their microbial partners. At any rate, as a unctional whole,there is much to be said or thinking o the whole community thattravels around with me a s a single composite entity.

I have mentioned that microbes remain by ar the most versatileand eective chemists in the biosphere. The ability o multicellularorganisms like ourselves to process ood is entirely dependent on theircooperation. Being high on the ood chain, we humans tend to con-sume highly processed oods that require less help rom our micro-bial symbionts to metabolise than would more challenging inputs. Itis worth recalling, though, that i we eat, say, cows, the amino acidswe absorb were synthesised by microbes in one o the our stomachso the animal, and i perhaps or moral reasons we preer to get ouramino acids rom beans, this is only possible due to the nitrogen-x-ing activities o bacteria associated with the roots o these plants. At

any rate, as is amiliar to users o powerul antibiotics, deciencies inour gut bacteria are a serious problem even or human digestion.

Let me add a brie word about plants in this context. The best-known metabolic capacity o plants is t he ability o their long captivemicrobial symbionts, chloroplasts, to capture the energy o sunlight.But plants also eed through their roots o course. And the roots o

28 J.F.Rawls,B.S.Samuel,J.I.Gordon,GnotobioticZebrafishRevealEvolutionarilyConservedResponsestotheGutMicrobiota, Proceedings of the National Acad-emy of Sciences, 101:596-601,200.

29 M.J. McFall-Ngai,M.J., Unseen Forces:the Influence of Bacteriaon Animal

Development,Developmental Biology22:1-1,2002.


20/28

38


39

second Lecture

a plant lie in the midst o some o the most complex multispeciescommunities on the planet. Bacteria and ungi not only orm densecommunities in the soil surrounding plant roots, but are also oundwithin the roots themselves. These ungi put out nutrient seekingtendrils, or hyphae, through the roots and i nto the outside soil. Thisis perhaps the most striking illustration o the idea that the inter-

ace between large multicellular organisms and their environments istypically mediated and essentially so by microbial communities.Given the permeation o the boundaries between ourselves and theexternal environment by comparably complex multi-species commu-nities, and their essential role in managing the chemical and cellulartrac across these boundaries, we should at least question our intui-tive sense that they are not part o us.

There is a theoretical ground or the assumption that an individ-ual should be taken to exclude its obligatory symbionts. This might bestated as the thesis, one individual, one genome. It is sometimes said,

or example, that a group o trees, originating rom the same root sys-tem, is reallyonly one individual. The motivation or this stipulationis an evolutionary perspective, according to which evolution involvesselection between genomes, but the stipulation is a problematic one.First, there are clearly important alternative perspectives that mustsometimes be accommodated. From an ecological perspective, orexample, we should surely preer one trunk, one tree. We might al sonote that even complex animals are to some degree genomic mosa-ics. In ext reme cases this may be t he result o abnormal reproductiveevents, as is known to the great cost o a ew human mothers whohave ailed genetic tests or parenthood o their children.30 Trans-plant surgery, including blood transusion, produces genomic mosa-

icism in some humans. More mundanely, mutation during develop-ment produces some genomic diversity, and in plants that reproducevegetatively or example by root suckers or rooting branches, thismay provide material or natural selection.

30 Thereareseveralcasesofmothershavinglostcustodyofchildrenonthegroundsthattheywereprovednottobethebiologicalmothersasaresultofdifferentpartsoftheirmosaicgenomesappearinginthechildandthegenetictestforpar-enthood.SeeH.Pearson,Humangenetics:Dualidentities,Nature1:10-11,2

May,2002.

It is also a amiliar act that the same genome may pertain to di-erent individuals. Close to home, we do not consider monozygotic,or so-called identical, twins to be a single individual. This drawsattention to the very important point, but not one I shall dwell ontoday, that there is much more to development than the unolding othe genome.31 But much more generally, we should again remind our-

selves o the elephant. The vast majority o organisms do not producean entirely novel genome in the process o reproduction. Althoughmicrobial genomes are extremely fuid over time, the basic process oreproduction is one o genome duplication. In short, the relationshipbetween genomes and organisms is not one to one, but at least one tomany. I want to suggest that it is a urther but well motivated step toadmit this relationship as many to many: not only can one genomebe common to many organisms, but one organism can accommodatemany genomes.

I hope I have anyhow said enough to dispose o a simple criterion

that might give a simple answer to the question, What is an organ-ism? The correct answer, I suggest, requires seeing that there are is agreat variety o ways in which cells, sometimes genomically homoge-neous, sometimes not, combine to orm integrated biological wholes.The concept o multicellular organism is a complex and diverse onewhich, incidentally, provides no conceptual obstacle to the broaderconception o the human i ndividual sketched above.

The broader ramications o this suggestion are once again bestdiscerned by looking more closely at the elephant. I have describedmicrobes as single-celled organisms, and this is how the organismsto which I wished to reer are generally conceived. However there are

compelling grounds or revising this view. Microbes are most com-monly ound as parts o communities, containing either one or many

31 Thispointhasbeenfundamentaltorecentcritiquesofclassicalmodelsofevolu-tion,fromthemid-twentiethcenturysynthesistoDawkinssgeneselectionism.SeetheDevelopmentalSystemsTheorydevelopedinS.Oyama, The Ontogeny ofInformation: Developmental Systems and Evolution, Cambridge:CambridgeUniver-sityPress,1986;andS.Oyama,P.E.Griffiths,andR.D.Gray(eds.),Cycles of Con-tingency: Developmental Systems and Evolution, Cambridge,Mass.:MITPress,2001.Forapplicationofthisperspectivetocriticismofevolutionarypsychologicalthe-oriesofhumannatureseemyHumanNatureandtheLimitsofScience,Oxford:

OxfordUniversityPress,2001.


21/28

0


1

second Lecture

distinct t ypes o microbe, communities which approximate many othe amiliar eatures o multicellular organisms.32

There are a number o converging types o evidence that sup-port this perhaps surprising proposal. Probably the most impor-tant has been mentioned, the requency o genetic exchange between

microbes, particularly within associated communities o microbes.An increasing number o biologists are beginning to suggest that thegenetic resources o a microbial community should not be thoughto as partitioned into individual genomes in individual cells, but arerather a community resource, a genetic commons.

The project o metagenomics, the attempt to collect al l the micro-bial genetic material in entire environments has become quite widelydiscussed, not least due to its association with Craig Venter, theleader o the ree enterprise wing o the Human Genome Project, anda larger than lie gure in contemporary biology. Venter embarked

on a well-publicised expedition around the worlds oceans collect-ing microbial genetic material rom the water.33 This is sometimesseen as no more than a collecting or gene-prospecting exercise, andindeed Venter discovered an astounding quantity o unamiliargenetic material and many previously unamiliar types o microbes.But as suggested by my reerence to a genetic commons, and by thegreat mobility o genetic material between microbial cells, it is but asmall step rom the metagenome, this totality o local genetic mate-rial, to the metaorganism, a multicellular organism composed o thecommunity o microbes that shares this resource.

The clearest context in which to present the idea o microbial

metaorganisms is with the phenomena o biolms. Biolms areclosely integrated communities o microbes, usually involving anumber o distinct species, which adhere to almost any wet surace.Biolms are ubiquitous, rom the slimy rocks and stones ound underwater and the chemically hostile acid drainage o mines, to the i nter-nal suraces o drinki ng ountains and catheters; indeed biolms are

32 J.A.Shapiro,(1998),ThinkingaboutBacterialPopulationsasMulticellularOrgan-isms,Annual Review of Microbiology,52:81-10,1998.FordiscussionseeOMalleyandDupr,op.cit.

33 J.C.Venter,etal.,EnvironmentalGenomeShotgunSequencingoftheSargasso

Sea,Science30:66-,200.

where most microbes generally like to be.34 In addition to the geneticexchange already discussed, the constituents o biolms exhibitcooperation and communication. These are most clearly exempliedby the phenomena o quorum sensing, in which microbes are able todetermine the numbers o cells in their communities and adjust theirbehaviour including reproduction in appropriate ways. The gen-

eral idea can perhaps be best appreciated by quoting a scientic paperon a very amiliar kind o biolm:

Communication is a key element in successul organizations.The bacteria on human teeth and oral mucosa have developedthe means by which to communicate and thereby orm success-ul organizations. These bacteria have coevolved with their hostto establish a highly sophisticated relationship in which bothpathogenic and mutualistic bacteria coexist in homeostasis. Theact that human oral bacteria are not ound outside the mouthexcept as pathogens elsewhere in the body points to the impor-

tance o this relationship. Communication among microorgan-isms is essential or initial colonization and subsequent biolmormation on the enamel suraces o teeth and requires physi-cal contact between colonizing bacteria and between the bacte-ria and their host. Without retention on the tooth surace, thebacteria are swallowed with the saliva. Through retention, thesebacteria can orm organized, intimate, multispecies communi-ties reerred to as dental plaque.35

For readers unconvinced that these should be counted as multicel-lular organisms, I invite refection on the diversity o orms o mul-ticellularity. Most amiliar are the plants and animals, and it would

certainly be possible to enumerate a series o major di erences in theway these two prominent groups o organisms are organised. Or con-sider the third taxonomic group generally acknowledged to includemulticellular organisms, the ungi. Fungi are generally divided intosingle celled organisms, yeasts, and a variety o multi-celled orms,such as mushrooms. But the multicellularity o ungi is a rather

3 Thisismoreclearlytrueofterrestrialthanpelagicmicrobes,verylargenumbersofthelatterbeingfoundasindividualplanktoniccells.However,italsoappearsthatahighproportionoftheseareinaninertstate,andonlybecomeactiveinthecontextofmicrobialcommunities.

35 P.E.Kolenbranderetal.,CommunicationamongOralBacteria,Microbiology and

Molecular Biology Reviews, 66:86-505,2002.


22/28

2


3

second Lecture

simple matter. Fungi orm threadlike chains o cells, called hyphae,which generally exist in tangled mats, called mycelium. Some variet-ies occasionally organise their hyphae into much more ordered struc-tures such as the amiliar mushrooms that unction to disperse un-gal spores. This is a a r less complex orm o multicellularity than t hatexhibited by the many dierentiated cell types o plants or mammals.

A mushroom is actually much more similar to the ruiting structu reso such social bacteria as the myxobacteria, which also orm colo-nial structures not unlike mushrooms or purposes o spore disper-sal though the cooperative hunting o other bacteria also reportedin some species o myxobacteria perhaps suggests a more complexsociality than that o ungus cells. It is worth mentioning that somecomplex multispecies organisms have been amiliar or a long time,most notably the lichens, symbiotic associations o photosyntheticalgae or bacteria with a ungus. Anomalous rom the perspective oa traditional dichotomy between unicellular organisms and monoge-nomic multicellular organisms, these seem quite unproblematic rom

the point o view o a more comprehensive understanding o multi-cellularity.

Multicellularity, even in the traditional sense just mentioned, isan enormously diverse phenomenon. Cells o dierent kinds organ-ise themselves into a vast diversity o cooperative arrangements, withvariously rigid structure, developmental trajectories and so on. Whatis particular surprising or traditional biological thought in the caseo microbes, however, is that these cooperative ventures typicallyinvolve cells rom quite diverse parts o the traditional phylogenetictree though as I have suggested this is not really unusual even orthe more amiliar multicellular organisms. The diversity o multi-

cellular organisation should be no great surprise. Leo Buss, perhapsthe pre-eminent theorist o biological individuality, claimed some20 years ago that multicellularity had evolved independently around17 times.36 In act it is air to say that orming cooperative associa-tions is very unda mentally what cells do. It is worth considering, assome biologists indeed have, that while no doubt evolution dependson competition among cells, it may be that what they primarily com-pete over is their ability to cooperate with other cells.37 Altruism, in

36 L.W. Buss, The Evolution of Individuality, Princeton: PrincetonUniversity Press,198.

3 L.Margulis,Symbiotic Planet: a New Look at Evolution. NewYork:BasicBooks,

1998

its technical biological sense o assisting another organism at somecost to onesel, ar rom being a undamental problem or evolution-ary biology, may turn out to be ubiquitous in the living world.38 Fromthis perspective, the diverse communities that make up microbialbiolms and even t he diverse communities that constitute a properlyunctional plant or animal, including its mutualistic microbial com-

munities, can quite properly be considered multicellular organisms.

Throughout these lectures, the one level o biological organisationI have constantly reerred to without qualication is the cell. And inact it does seem clear that t his is the most unproblematic such level.I there were any unique answer to the question, what are t he constit-uents o lie? that answer would have to be cells. Cells are enormouslydiverse things, o course, but everything on the standard representa-tion o the tree o lie is a cell or is composed o cells. The problems Ihave indicated with a nave conception o the organism derive romthe complexity and diversity o the relations among very diverse sets

o cells, but they do not problematise the idea o the cell as the basicconstituent o these various associations.

I have to note, however, that hiding behind my now amiliar ele-phant is yet another elephant. I have hardly mentioned the livingorms that are not cellular and that are even more numerous thanthe cellular microbes, namely the viruses and related objects. Viruseshave been ound associated with every organism studied and theyoutnumber any other class o biological entities by at least an order omagnitude. Estimates o the numbers o viruses on Earth are in therange o 10 to the power o 31 a 1 ollowed by 31 zeros.39 This num-ber is probably incomprehensible to non-mathematicians: it has been

described by one virologist as amounting to 250 million light yearso viral genes placed end to end.40 The number o viruses on Earthprobably exceeds the number o cellular microbes by at least an ordero magnitude.

38 Alessradicalbutstill controversialclaimfortheprevalenceofaltruism,groundedinbroadlyconventionalevolutionarythinking,isE.SoberandD.S.Wilson,UntoOthers: The Evolution and Psychology of Unselfish Behavior,Cambridge,Mass.:Har-vardUniversityPress,1998.Thepresentsuggestiondepartsconsiderablyfurtherfromthewidespreadscepticismaboutcooperation.

39 F.Rohwer,andR. Edwards,ThePhageProteomicTree:aGenome-BasedTax-onomyforPhages, Journal of Bacteriology, 18:529-535,2002.

0 G.Hamilton,Virology:TheGeneWeavers,Nature1:683-685,8June2006.


23/28


5

second Lecture

It is sometimes said that viruses are not living things at all. And itis true that they oten exist in an entirely static state in an inert crys-talline orm that can hardly be said to be living. On the other handthey are the most ecient replicators o their genetic material onEarth. It has been estimated that anything up to 50% o marine bac-

teria are killed every day by pathogenic viruses, phages, and in thisprocess the hostile virus produces thousands o replicas o itsel oreach bacterium it destroys.41 It has been suggested that perhaps tento the power o 24 viruses are produced on Earth every second. Andthese massive replication rates are tied to high mutation rates andalmost unlimited mutation mechanisms. Viruses can thus evolve atrates that are ar beyond even what is possible or cellular microbes.It is a amiliar observation that the HIV virus evolves signicantlyin the body o a single host, a act t hat provides enormous obstaclesto the development o eective therapies. When compared with ourown 20-30 year generation spans, populations perhaps 22 orders omagnitude smaller, and handuls o ospring, it is clear that viruseshave abilities to explore the space o chemical possibility that organ-isms such as ourselves could hardly dream o. It is thus no surprisethat viruses are the greatest producers and reservoir o genetic diver-sity on Earth.

Even more interesting than the viruses that kill their hosts arethe ones that dont. Most viruses live in stable relations with theirhosts but all viruses reproduce themselves by exploiting the chemi-cal resources o their hosts, and many also insert their genetic mate-rial into the host genome. Since they may also incorporate DNA romtheir hosts genome into their own, they can readily transer DNA

rom one organism to another. Although viruses are generally quitespecic in their hosts they can, as is well-known, transer to newhosts. When they do this they can transer DNA rom one species oorganism to another. I mentioned earlier the so-called junk DNA thatmakes up most o the DNA o eukaryotes such as animals or plants.As well as being increasingly clearly not junk, this is in act materialmainly or entirely o viral origin.42 It has been noted, or example,that the main dierences between human and chimpanzee genomes

1 M.Breitbart,andF.Rohwer,HereaVirus,ThereaVirus,EverywheretheSameVirus?,Trends in Microbiology,13:28-28,2005.

2 L.P.Villarreal,CanVirusesMakeUsHuman?,Proceedings of the American Philo-

sophical Society, 18:296-323,200.

are not, as might have been supposed, in coding sequence, but in non-coding regions derived originally rom viruses.43 The enormous pow-ers o viruses to evolve and their ability to insert genetic material intothe genomes o cellular organisms has led some biologists to specu-late that it is viruses that are the prime movers o major evolution-ary change or, at any rate, the main providers o novel biochemical

resources. It is beginning to seem possible that, just as microbes arethe expert metabolists in nature, so viruses are the leading evolvers.And as microbes provide us with indispensable chemical services, itmay be that v iruses provide us with comparably signicant evolution-ary services. At any rate, without disputing the undamental impor-tance o cells as oci o causal power and organisation that make pos-sible the complex biological structures and communities which wemost naturally think o as biological objects, it is important not toorget the much larger number o non-cellular biological objects thatspend their time moving genetic material into and between cells. Theextraordinary biological capacities o microbes and viruses pose avery interesting question as to what it is that amiliar multicellularorganisms do well enough to exist at all unless, indeed, to adapt awell-known idea o Richard Dawkins, they are vehicles or carryingtheir microbial masters around, or niches constructed as residencesor microbial communities.

v

My message so ar may seem discouraging with regard to the pros-pects o real biological understanding. It is true that the very abilityto discern the complexities I have sketched in these lectures d isplaysthe remarkable power o the instruments scientists have devised toexplore the workings o lie. Scientists have revealed in exquisitedetail the st ructures o biological molecules and their modes o inter-action with other molecules. And they are compiling comprehensiveinventories o these molecules. Yet the sheer number o constituentsthus discovered combined with two other problems that I have triedto emphasise throughout these lectures, presents a problem o al most

3 Villarreal,op.cit.


24/28

6


second Lecture

inconceivable complexity. The rst problem is that even as we dis-cern these multitudinous constituents o living things, their biologi-cal signicance cannot be u lly discerned without a view both o thecausal powers derived rom their own structure and the causal pow-ers o the larger systems in which they participate. We cannot prop-erly appreciate the biological properties o a virus or a bacterium, say,

without understanding both the chemical processes ound within itand the much larger systems o which it is a vita l constituent. The sec-ond problem is that even the inventory o causally signicant objectsat a particular level is not something u lly determined by nature, butmay vary according to the kind o question we want to ask. Nature isnot divided by God into genes, organisms or species: how we chooseto perorm these div isions is theory relative and question relative.

It is, then, possible to achieve remarkable insights into lie pro-cesses, but is there any way we can ever hope to t them together intoan integrated understanding o how a living thing, even a single liv ingcell, unctions? There is an exciting project that is currently receivinga lot o attention and investment and which does have this aspiration,integrative systems biology. I shall now say a ew words on this topic.

First, what is systems biology?44 It is oten said that it is nothingnew. General systems theory is generally traced to Karl Ludwig vonBertalany in the mid twentieth century, and a number o biolo-gists, perhaps most notably the American theoretical biologist RobertRosen, have developed ideas that were at least important precursorso contemporary systems biology.45 At another extreme I have heardbiologists say that systems biology is no more than a new name orphysiology. The dierence, I think, and perhaps this is a case where

a dierence o degree becomes a dierence o kind, is the vast quan-tity o data, especial ly molecular data, that is available to the currenttheorist. Indeed it is not too cynical to say that a major motivationor this entire project is the question, now that we have all these tera-bytes o molecular

Date post:	07-Apr-2018
Category:	Documents
Upload:	taimurorg
View:	220 times
Download:	0 times

Spinoza Lectures: Constituents of Life by John Dupré

Documents