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ORIGINAL ARTICLE

Regenerative medicine: stem cells and the science ofmonstrosityM Cooper. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

J Med Ethics; Medical Humanities 2004;30:1222. doi: 10.1136/jmh.2003.000137

The nineteenth century science of teratology concerneditself with the study of malformations or monstrosities, asthey were then called. The first major contribution to thefield was the work of Isidore Geoffroy Saint-Hilaire,Histoire Generale et Particulie`re des Anomalies delOrganisation chez lHomme et les Animaux, published in1832, whose classifications formed the basis for the laterexperimental science of teratogeny, the art of reproducingmonstrosities in animal embryos. In this article, I will arguethat recent developments in the field of regenerativemedicine can be situated in the tradition of teratologicaland teratogenic studies dating back to the nineteenthcentury. In particular, I will be interested in the historicallink between studies in teratogenesis (the artificialproduction of teratomas) and stem cell research. Recentadvances in stem cell research, I will suggest, return us tothe questions that animated nineteenth centuryinvestigations into the nature of the monstrous or theanomalous. In the process, our most intuitive conceptions oflife itself are undergoing a profound transformation.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Correspondence to:Melinda Cooper,Department of Sociology,Division of Society,Culture, Media andPhilosophy, MacquarieUniversity, NSW 2109,Australia; [email protected]. . . . . . . . . . . . . . . . . . . . . . .

INTRODUCTIONOne of the more curious offspring of nineteenthcentury biology was the science of teratogenyascience which concerned itself with the causallaws of malformations or monstrosities. Tera-tology grew out of the epigenetic tradition of thelater eighteenth century and received its firstcomprehensive formulation in the biologicalphilosophy of Etienne Geoffroy Saint-Hilaire. In1822, Etienne issued a second volume to hismajor work, Philosophie Anatomique, in which heextended his inquiries to include the laws ofanatomical composition involved in the produc-tion of human monstrosities.1 The secondvolume of the Philosophie Anatomique representedthe first detailed work of classification specifi-cally dedicated to malformations, and the first toplace the study of monstrosity at the very centreof a larger philosophy of nature. In 1832,Etiennes son, Isidore, published his threevolume Traite de Teratologie, which systematisedand extended upon his fathers founding work.2

It was Isidore who invented the term tera-tology and declared the science of mon-strosity an autonomous and even foundational

discipline within the larger field of morpho-logical anatomy.From its inception, the science of teratology

was associated with the more ambitious projectof producing artificial monstrosities throughexperimentation on animal embryos. BothEtienne and Isidore record various inconclusiveefforts to reproduce monstrosities through themanipulation of fertilised chicken eggs. For moredetail on these experiments see Appel T A andOppenheimer J A.3 4 These experiments werelater carried out with more success by CamilleDareste, who credited himself with the inventionof the biotechnological art of teratogeny, theexperimental counterpart to teratology. Darestes1871 work, Recherches sur la Production Artificielledes Monstruosites ou, Essais de TeratogenieExperimentale, details experiments in which heset about producing all of the monstrosities listedby the teratologists and raises the possibility ofcreating wholly new varieties.5

The teratological tradition carried on into thetwentieth century, but its conceptual relation tothe problem of monstrosity was more often thannot forgotten. Today teratology is simply thescience that deals with abnormal developmentand congenital malformations, without referenceto monstrosities, and is the one [definition]accepted by the biomedical world.6 In thisarticle, I will argue that recent developments inthe field of regenerative medicine can be situatedin the tradition of teratological and teratogenicstudies dating back to the nineteenth century. Inparticular, I will be interested in the historicallink between studies in teratogenesis (theartificial production of teratomas) and stem cellresearch. Recent advances in stem cell research, Iwill suggest, return us to the questions thatanimated nineteenth century investigations intothe nature of the monstrous or the anomalous.In the process, our most intuitive conceptions oflife itself are undergoing a profound transfor-mation.

NORMALISING THE MONSTROUS?CONCEPTS OF THE PATHOLOGICAL INNINETEENTH CENTURY BIOLOGYPerhaps the most comprehensive study of nine-teenth century conceptions of the normal, thepathological, and the monstrous can be found inthe work of the philosopher of science, GeorgesCanguilhem. In two texts, The Normal andthe Pathological and Monstrosity and theMonstrous, Canguilhem situates the science ofteratology within the larger historical context ofbiomedical approaches to the pathological.7 8

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For Canguilhem, the most important innovation of thenineteenth century life sciences lies in the radical negation ofany positive, irreducible concept of pathology, sickness ormonstrosity. In a study of the work of Auguste Comte andClaude Bernard, he traces the formation of a theory ofphysiology according to which the pathological phenomenafound in living organisms are nothing more than quantitativevariations [of the norm], greater or lesser according tocorresponding physiological phenomena (Canguilhem G,7

p 13). The normative bias of nineteenth century biologydenied any qualitative specificity to the pathological. Illnessand health could no longer be figured as two essentiallyhostile, incompatible forces, but came to be identified asmere quantitative variations in a continuum of biologicalphenomena all subject to the same physiological laws. As aconsequence, the pathological became strictly measurable; itwas located in any physiological phenomenon differing inintensity, by excess or default, from the normal state.In the work of Auguste Comte, the qualitative identifica-

tion of sickness and health was derived from Broussaisstheory of excitation, where disease was defined as theexcess or lack of excitation in the various tissues above orbelow the degree established as the norm (Canguilhem G,7

p 17). In the work of the physiologist Claude Bernard, thisreduction of the pathological to a variation on the normalwas integrated into a homeostatic model of the organism. ForBernard, the various processes of organic metabolism wereconditional upon a complex system of internal regulativemechanisms, normally tending towards equilibrium. TheBernardian principle of organic self regulation led to theformulation of a therapeutic science, whose aim wasessentially restorative. If the pathological could be measuredin so far as it produced disequilibrium, the therapeuticintervention of the medical sciences could only seek to re-establish those homeostatic mechanisms that had momenta-rily been disturbed by illness.9

In the conclusion to his study on the normal and thepathological, Canguilhem argues that one of the conse-quences of nineteenth century biology, in its attemptto reduce the pathological to a mere quantitative dif-ference, was a tendency to eradicate the experience of illnessitself:

The need to re-establish continuity in order to gain moreknowledge for more effective action is such that theconcept of disease would finally vanish. The convictionthat one can scientifically restore the norm is such thatin the end it annuls the pathological (Canguilhem G,7

p 13).

At the same time, and for the very same reason, hecontends, the experimental study of pathological phenom-ena, ranging from illness to monstrosities or deformities,acquired an unprecedented importance as a means ofilluminating the science of health.In the life sciences of the nineteenth century, pathological

phenomena came to operate as a kind of in vivo experimentalconfirmation, by default, of the operations of the norm. It isin this sense, Canguilhem argues, that the science ofteratology, although ostensibly engaged in the investigationof monstrosities, actually exploited these models as a kind ofexperimental demonstration of the theory of biologicalnormativity. In the work of Comtefor example, the studyof pathology in the form of deformities or monstrosities canbe understood as an extreme but perfectly logical extensionof the study of illness. Monstrosities were perhaps moreradical deviations from the norm, but they could only beunderstood and exploited in its shadow:

the study of anomalies and monstrosities conceived asboth older and less curable illnesses completes the study ofdiseases: the teratological approach [study of monsters]is added to the pathological approach in biologicalinvestigation (Canguilhem G,7 p 20).

But Canguilhems rather schematic interpretation of nine-teenth century biology does not seem to do justice to thealternative conceptions of the monstrous which coexistedwith, and seriously undermined, the normative precepts ofBernardian science. This is particularly evident in his cursorytreatment of the father and son, Etienne and Isidore GeoffroySaint-Hilaire, who can be credited with founding the nine-teenth century science of monstrosity. In a text devoted to thehistory of the monstrousfor example, Canguilhem notesthat the science of teratology can be traced back to EtienneGeoffroy Saint-Hilaires occasional texts on monstrosity butreceived its most definitive formulation in his son Isidoresmajor work of classification, Histoire Generale et Particulie`re desAnomalies de lOrganisation chez lHomme et les Animaux. It is tothis text that he attributes the final domestication of themonstrous. Hereafter, he argues, earlier notions of themonstrous, with their bizarre alliance of the fantastic andthe medical, gave way to a strictly normative understandingof the relationship between the normal and the pathological:

Hereafter, monstrosity appears to have given up the secretof its causes and laws; the anomaly, it appears, is calledupon to provide the explanation of the formation of thenormal. Not because the normal is only an attenuatedform of the pathological, but because the pathological isthe normal that has been hindered or pushed off course.Take away the hindrance and you obtain the norm(Canguilhem G,8 pp 1801).

Canguilhems work on the normal and the pathological hasexerted an unmistakable influence over subsequent studieson the subject of monstrosity in the life sciences. Inparticular, his thesis that the invention of teratology as anautonomous scientific field represents a move towards acausal philosophy of the monstrous and hence a definitive actof normalisation, a kind of scientific disciplining of theirrational forces of the maternal imagination, has beencorroborated by all but a few studies. One of the mostinfluential of these is that of Marie-Hele`ne Huet, MonstrousImagination,10 which uncritically adopts Canguilhems viewson the nineteenth century concept of the monstrous (HuetM-H,10 pp 1012).It is precisely on this point, however, that I would question

Canguilhems historical account. In the life sciences of theearly nineteenth century, the precise nature of the monstrouswas an object of unresolved debate, where the mostnormative conceptions of life came into conflict with themost anomalous. Etienne Geoffroy Saint-Hilaires theory ofmaterial composition depends precisely on a concept of theanomalous as an autonomous generative principle, onto-logically prior to the distinction between the normal and thepathological.The work of both Etienne and Isidore Geoffroy Saint-

Hilaire represents a countertradition within the life sciencesof the nineteenth century, a counterphilosophy of themonstrous which points to recent directions in the field ofstem cell research.

UNITY OF COMPOSITIONTHE MONSTROUS ANDTHE ANOMALOUSIn the early years of the nineteenth century, Etienne GeoffroySaint-Hilaire was famous for having elaborated a philosophy

Regenerative medicine: stem cells and the science of monstrosity 13



of anatomy which refused to draw on analogies of form andfunction in the classification of animals. Instead, hedeveloped a method of comparative morphology which reliedon the principle of unity of compositionthe idea that thedifferences and proximities between living structures shouldbe understood as so many actualisations of the one, commonplane of composition. For Etienne Geoffroy Saint-Hilaire, thepoint was not to determine the ideal form or function of anorganism, from whence to deduce its possible deviations ormonstrous anomalies, but rather to search for the geo-metrical principles of composition themselves, in all theirpossibilities. In other words, Geoffroy Saint-Hilaire taughtthat all possible structures could be related to each otherthrough varying degrees of transformation. All variations ofform, he argued, participated in the one abstract plane ofcomposition, the one topological space of infinitely deform-able relations. It follows that the normative distinctionbetween the normal and the pathological is strictly incom-prehensible within the terms of Geoffroy Saint-Hilairesphilosophy. Etiennes son, Isidore Geoffroy Saint-Hilaire,clarified this point when he distinguished between theabnormal and what he referred to as the anomalouswhereas the abnormal represents a deviation from the norm,a difference that can only be defined negatively in relation tothe norm, the anomalous belongs to an order of abstractcomposition which precedes the very distinction between thenormal and the pathological (Geoffroy Saint-Hilaire I,2 pp567). Etienne argued that what are known as monstrositiesrepresent varying degrees of transformation in the materialstructure of an organismin this, they are no different fromthe bodies we call normal. Because, however, they materialisein non-habitual postures which may occur in the early stagesof embryogenesis but are not often visible in the later stagesof development, he accords them a special pedagogical value.A report on his work carried out by the Royal French Academyof Science, which is cited in Cahn T, recounts that:

Ever since Monsieur Geoffroy Saint-Hilaire was led toconsider facts relative to monsters as so many experi-ments, as it were, prepared in advance by nature in orderto show physiologists the means which give rise to organiccompositions, he has continued to carry out research onthese deviations of organisation. In effect, according to theauthor, the study of organisation in its irregular acts, andof nature caught as it were by surprise in moments ofhesitation and impotence, offers a very instructivespectacle. Whoever, he adds, has taken stock of all thepossible modifications of organisation, recognises thatthe diverse forms in which it manifests itself derive fromthe same type; he therefore does not regard thesemonsters, as Aristotle did, as exceptions to general laws,nor does he believe, like Pliny, that nature produces themto astonish us and have fun, rather he considers them asunfinished sketches, as representing differing degrees oforganisation.11

Between 1821 and 1830, Etienne published thirty articleson the subject of monstrosity. For an overview andbibliography of these articles see Cahn Ts La Vie et lOeuvrede Etienne Geoffroy Saint-Hilaire (Cahn T,11 pp 16785, 296310). But the most extensive exposition and development ofEtiennes theses on monstrosity can be found in the laterwork of his son, Isidore, Histoire Generale et Particulie`re desAnomalies de lOrganisation chez lHomme et les Animaux, desMonstruosites, des Varietes et Vices de Conformation, ou Traite deTeratologie, published in 1832.2

In particular, Isidore developed his fathers intuition thatthere existed a crucial relationship between the morphological

plasticity of the early embryo and the strange contortionsto be seen in the body of the monstrosity.Isidore argued that the transformative power of composi-

tion of the anomalous is most visible, in developmentalterms, in the very early stages of embryogenesis. The embryotraverses transformations at a speed which we are barely ableto apprehend, and simultaneously embodies states which willbecome mutually exclusive in the later development of thefetus. Here he points to the coexistence of the male andfemale sexual organs in the early stages of embryogenesisand to the mutations of form which seem to fleetinglymaterialise the shapes of other species. In the very earlystages of development, it seems, the different possibilities ofcomposition which will later be defined in restrictive terms asso many mutually exclusive paths of differentiation, are ableto coexist.Drawing on his fathers work on arrested and retarded

development, Isidore Geoffroy Saint-Hilaire accounted formonstrosities as a stage of embryonic development whichhad become suspended in time or lagged behind the rest ofthe body. The organs and functions which would later bedifferentiated in the progressive unfolding of developmenthad here been freeze framed in an incongruous coexistence ofthe embryonic and the mature. Monstrosities, he concluded,offer us a material insight into the transformative possibi-lities of the anomalous. They represent not so much adeviation from the norm but rather the partial actualisationof another order of composition altogetherthe anomalous:

Up until then, the phenomena of monstrosity had beenconsidered as nothing more than irregular arrangements,bizarre and disordered formations; vain spectacle bywhich nature amused itself by making fun of its observersand liberating itself from its ordinary laws. [The theory ofphilosophical anatomy] replaces the idea of bizarre,irregular beings with the truer, more philosophical one ofbeings obstructed in their development, where organs ofthe embryonic stage, preserved until birth, have come tobe associated with organs of the fetal stage. Monstrosity isno longer a blind disorder, but another, equally regular,equally lawful order; or rather, if one prefers, it is themixture of a former order and a new order, thesimultaneous presence of two states which, ordinarily,succeed one another (Geoffroy Saint-Hilaire I,2 p 18).

It is also because of their mutual participation in thepowers of composition of the anomalous that GeoffroySaint-Hilaire predicts the future interdependence betweenstudies in embryology and teratology. All monstrosities, heclaims, are to some degree permanent embryos, livinganachronisms that preserve as if suspended in time the stagesof early embryological development:

From this moment too, the science of monstrosities isintimately linked to anatomy, and especially with thatbranch of anatomy which is concerned with the laws ofdevelopment and the order of appearance of our organs.Monsters, according to the new theory, are in somerespects permanent embryos; they show us the emergenceof simple organs just as in the first days of their formation;as if nature had halted its course in order to provide ourtoo slow observation with the time and means toapprehend it. In the future, therefore, the science of mon-strosity cannot be separated from embryogenesis; it willusefully contribute to its progress andwill receive no less con-siderable services in return (Geoffroy Saint-Hilaire I,2 p 19).

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It is not surprising then that Isidore reserves a special placefor what he calls parasitic monstrositiesembryonic growthsthat can remain indefinitely within their mothers body, inthe ovaries or uterus, sprouting hair, fatty tissue, teeth, andcartilage in a strange living caricature of the normal embryo.Isidore approaches the parasitic monster with an unmistak-able sense of fascination. He readily admits that medicalscience offers little insight into these monstrosities, oftenconsidered as mere waste products, and yet he dedicates overthirty pages to their description and places them at the veryend of his list of developmental anomalies because, in hisopinion, they represent the most anomalous of growths:

Anatomists have long been aware that we sometimes find,either in the uterus or the ovaries or even in some otherpart of the body, diverse organic parts such as teeth oreven varying amounts of bone, held together in a veryirregular and often totally formless mass. The history ofthese singular productions has remained very obscure;and perhaps their complete explication will continue toelude the explanations of physiologists for a long time tocome. However, even now it is possible to demonstrate, aswe shall see, that at least in some cases, these organicparts which have developed in the uterus or ovaries arenothing but products of conception that have remainedsingularly imperfect, new beings whose formation,initiated or subject very early on to the influence of veryanomalous circumstances, has been powerfully obstructedor diverted in a very warped direction (Geoffroy Saint-Hilaire I,2 pp 5367).

Firstly and most obviously, parasitic monstrosities areanomalous from a morphological point of view. Althoughthey grow and differentiateGeoffroy Saint-Hilaire lingersover the details of sprouting hair and sets of teeththey neveracquire the regular morphological form of the organic body.Indeed, he comments, they are not so much bodies as clustersof tissue. Their form is strictly speaking indeterminable:

Not only does their form deviate considerably from thecommon type but it is absolutely indeterminable. Theircluster [ensemble]for body is hardly a word that can beapplied to these confused massesis composed only of afew organic parts, mostly a few bones or teeth in variousgroupings, often accompanied by fat and hair, andadhering, without the intermediary of an umbilical cord,to the organs of the mother, or perhaps sometimes in a fewcases to a very imperfect and more or less completely un-recognisable placenta (Geoffroy Saint-Hilaire I,2 p 5378).

More obscurely, Geoffroy Saint-Hilaire points to evidencesuggesting that the parasitic monster does not necessarilyhave to die. All monstrosities, he contends, can be consideredto some degree as permanent embryos, embodying frozenmoments of early embryological development. The parasiticmonster, however, reveals the extreme potentialities of theanomalous in the sense that it appears capable of prolong-ing almost indefinitely its life in the womb of its mother(Geoffroy Saint-Hilaire I,2 p 564). The parasitic monster is theproduct of a pregnancy that never comes to term, aninterminable and bizarrely disorganised gestation:

In relation to the mother, they therefore remain as youngembryos; and as this latent and completely embryonic lifeis sufficient for such simple beings, they are neitherexpelled from the uterus, if they have developed in this

organ, nor, if they have formed in the ovaries, tubes orabdomen, do they perish as a result of ineffectual birthspasms, just like those extrauterine fetuses which do notsuccumb in the first months.

Parasitic monsters are thus permanent embryos whosegestation has no term (Geoffroy Saint-Hilaire I,2 p 564).

What Isidore Geoffroy Saint-Hilaire is describing here is atype of ovarian tumour which would come to be known as ateratoma in the latter part of the nineteenth century (theterm teratoma, which literally means monster tumour, wasfirst coined in 1863). For a detailed history of the teratoma,see History of teratomas by J E Wheeler.12 Teratomas have along medical history. Fragmentary accounts of visibleteratomas (in the testes or the spine of newborn infants)can be found in ancient tablets. The first well documentedcase of an ovarian teratoma can be traced back to theseventeenth century, when the dissection of corpses hadbecome commonplace. A medical text published in 1658describes and illustrates an ovarian teratoma sprouting aclump of hair.13 In the nineteenth century, reports of ovariantumours, containing lurid details of teeth, weight and hair,became more frequent. The genesis of teratomas, however,remained controversial. Once thought to arise from night-mares or communion with witches or the devil, teratomasretained a connection with perverse sexuality in the medicalaccounts of the nineteenth century. Geoffroy Saint-Hilairefor example, cites contemporary theories attributing theparasitic monster to excessive masturbationsuch theorieswere able to account for the existence of parasitic monsters invirgin or prepubescent girls and old women. BecauseGeoffroy Saint-Hilaire insists, however, on attributing themto a veritable act of generation involving fertilisation, heexcludes these cases from his overview (Geoffroy Saint-Hilaire I,2 pp 55660). Parasitic monsters, he argues, must beconsidered as true products of conception.It was not until the latter part of the twentieth century that

biologists returned to the question of the genesis ofteratomas, in the context of investigations into germ celldevelopment, differentiation, and cancer. It was these studiesthat established a link between ovarian teratomas andparthenogenesisconfirming Geoffroy Saint-Hilaires thesisthat the teratoma is indeed the product of a veritable act ofgeneration, but one which does not involve the union of eggand sperm. It was from these studies also that thecontemporary field of stem cell research emerged. The historyof stem cells, in other words, can be traced back toexperiments in teratogenesisthe artificial production ofmonstrous growths in animals.In what follows, I will look at the teratogenic experiments

which emerged from Etienne and Isidore Geoffroy Saint-Hilaires founding work on teratology, and suggest aconceptual affiliation between these early experiments inthe production of monstrosities and the recent history ofstem cell research.

EXPERIMENTAL TERATOGENYCREATING THEMONSTROUSIn his 1871 work, Recherches sur la Production Artificielle desMonstruosites ou, Essais de Teratogenie Experimentale,5 CamilleDareste, the founder of the experimental science of terato-geny, expresses his intellectual debt to Etienne and IsidoreGeoffroy Saint-Hilaire, the first anatomists to have system-atically studied the question of monstrosity.In Darestes work, however, there is a shift in perspective.

Whereas Etienne and Isidore Geoffroy Saint-Hilaire wereinterested in the infinite possibilities of transformation which




exist in virtual form in the abstract plane of compositionunderlying all material structures, Dareste looks towards thefuture evolution of life, in which these transformations willunfold as so many new, unpredictable inventions. ForDareste, the anomalous is not so much an ontologicalprinciple as a time arrow of innovation (although of coursethe two perspectives are not mutually exclusive). Heconceives of evolution as an expanding horizon of variability,an open ended exploration of the possibilities of life, in whichthe experimental science of teratogeny participates:

Whereas observation only gives us a knowledge of actualrealities, experimentation, thanks to its creative power,realises all that is possible; it thus opens up unlimitedprospects (Dareste C,5 p 42).

Like experimental chemistry, he claims, teratogeny shouldaspire to become a science of all possible bodies, implyingan unlimited variability of forms (Dareste C,5 p 2443). Hisinterest in the time arrow of evolution implies that theunlimited prospects of biological invention can no longer bededuced in the present, from the transformative possibilitiesinherent in all material structures, but can only be revealedin the future. In this sense, he questions whether suspended,arrested or excessive development account for all thepossibilities of invention. Pointing to the phenomenonof metamorphosis in insects, he asks whether suchdramatic reinventions of structure might be possible invertebrates:

Are arrested and excessive development the only mod-ifications that an organ can undergo? And isnt it possibleto conceive that an embryonic blastomere might, in thecourse of its evolution, acquire a form and a structure thatare completely different from the one it presents in itsnormal state? (Dareste C,5 p 200)

Darestes provisional response is that given the currentunderdeveloped state of experimental studies, it is impos-sible to establish in any definitive way the limits of thepossible (Dareste C,5 p 202).Writing in the latter part of the nineteenth century when

Darwins work had become available, but prior to the latersplit between embryology and Mendelian genetics, Darestewas able to draw connections between the teratologicaltradition and the Darwinian concept of inheritable variation.He quite explicitly presented his own teratological experi-ments as an extension of Darwins studies on planthybridisation and thus as a means of illuminating and eveninitiating the formation of new species and races from theproduction of monstrosities:

It [my research] demonstrates in the most complete mannerthe possibility of modifying, by the action of externalphysical causes, the evolution of a fertilised germ. Thedemonstration of this fact is of interest not only for theproduction of monsters but also for biology in its entirety.

In effect, if it is possible to produce monstrosities bymodifying the evolution of a fertilised germ, we mustconsider it possible to produce simple varieties, in otherwords slight deviations from the specific type, which arecompatible with life and the generative functions (DaresteC,5 p 41, p 42).

For Darwin, as for Etienne and Isidore Geoffroy Saint-Hilaire, although informed by different perspectives,

anomalous variation represented the very possibility ofinvention, without which life would be incapable oftransformation or evolution. Darwin after all insisted thatmonstrosities cannot be separated by any distinct line fromslighter variations and established their difference as one ofutility only.14 Monstrosity, according to Darwin, impliessome considerable deviation of structure, generally injur-ious, or not useful to the species, and by extension we coulddefine his concept of variation as entailing the production ofa useful or reproducible monstrositya monstrosity that works(Darwin C,14 p 34). The significance of this passage in relationto social conceptions of the normal and pathological, hasbeen analysed at length by the cultural historian E ONeill inher study, Raw Material: Producing Pathology in VictorianCulture.15 ONeill argues that scientific discourses of themonstrous were fundamentally distinct from the morefamiliar discourses of degeneration which flourished in thenineteenth century. Whereas the science of degeneration wasclosely associated with notions of racial and social hygieneand focused on the deformities of the labouring body, thescience of monstrosity presented the body as public spectacle,novel commodity, and innovation. In this sense, if the institu-tional context of the degenerate or abnormal body can betraced from the clinic, to the school and to the factory, andidentified with the mechanisms of discipline, as analysed byFoucault, ONeill argues that the monstrous body could befound simultaneously in the public science lecture, wheredeformities were put on display, and on stage in the freakshow. Far from attempting a normalisation of the degenerate, shecontends that the freak show presented the anomalous in itsproductive, regenerative, and even sublime possibilities.

The popularity of the freak show may have been a sign ofcultural degeneration, but the freaks themselves were,paradoxically, an allegory for the regenerative possibi-lities contained within the spectacle of decline. Indeed,what the freak show celebrates is a marvellously debasedimage of industrial existence, a mode of being sophenomenally degraded that it approaches the sublime.Monstrosity does not register defect as disease; instead itmakes human aberration into an advertisement for a newembodiment (ONeill E,15 p 193).

The result was a sort of assembly-line individualism, anendless procession of human oddities whose cumulativeimpact was to standardize abnormality itself, to reduce thescene of natures bounty to a series of predictable,replaceable originals (ONeill E,15 p 195).

In accord with ONeills thesis, my reading of the science ofteratology suggests that it offers a conception of the anomalous asprior to the normal, and reproducible as such.Throughout the Origin of Species, Darwin freely cites

examples from Geoffroy Saint-Hilaires classification ofembryological monstrosities and in the French version ofthe Descent of Man, he refers to Darestes experiments as fullof promise for the future. For Darwins references toGeoffroy Saint-Hilaire, see The Origin of Species (Darwin C,14

p 115, p 118, p 122). For Darwins remarks on Dareste, ascited by Dareste himself, see Darestes 1871 work, (DaresteC,5 p 46). Dareste, however, seems to be putting forward aLamarckian theory of acquired inheritance when he writesthat the heredity of all varieties of organisation, when theydo not impede the exercise of the generative functions, is nowestablished in the clearest of manners. It is the condition ofthe formation of races (Dareste C,5 p 41). The Lamarckiantheory of heredity was later discredited by the Neo-Darwinian

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school, which restricted inheritable variation to chancegenetic mutations. But in the context of current biotech-nological experiments it could be argued that we arereturning to a Neo-Lamarckian model in which acquiredtransformation becomes inheritable.Certainly, Darestes reflections on the future possibilities of

teratogeny are remarkably prescient. He noted that his ownexperiments intervened in the process of embryogenesis afterfertilisation while Darwins studies on plant selectionconsisted in the determination of particular crosses beforefertilisation. Neither of these methods, however, had as yetdeveloped ways of intervening into the germ cell (unfertilisedegg or sperm) itself (Dareste C,5 p 42 note 1). It was in thisdirection, he suggested, that experiments would need tomove if the production of monstrosity was to become a trulygenerative sciencea science, in other words, in whichmonstrosity would be put to work as the source of allpossible bodies.Recent studies on stem cells have indeed emerged from the

intersection of these two lines of inquiry. In the first place,stem cell research developed from the experiments interatogenesisthe artificial production of teratomas in mice.More recently, advances in cloning technologies have made itpossible to cultivate reproducible forms of the same experi-mental monstrosities, effectively combining interventioninto the germ cell with the manipulation of embryogenesis.This technique, known as somatic cell nuclear transfer,would involve a patient donating a somatic or non-reproductive cell which would then be cloned using anenucleated donor egg. The donor would effectively becomethe contemporary of his or her own (cloned) embryogenesis.The growth of this embryo would be deliberately deregulatedin order to produce specific cell types, which would then beavailable to the patient as a reserve of therapeutic tissue.Such a technique combines the teratogenic experiments ofDareste with interventions into the actual germ cell to createsomething that could be likened to a reproducible mon-strosity. For further detail on this technique, see PedersonRA.16

It is his interest in the experimental and controlledreproduction of monstrosity which establishes Dareste as alink between the science of teratology and recent advances inthe field of regenerative medicine. Like Darwin, whodefined the difference between variation and monstrosity interms of their ability to perform work, Darestes approach tomonstrosity is directly concerned with the problematic oftheir technical reproducibilitythe problem which of courseunderlies the massive development of genetic and otherbiotechnologies over the last few decades. He described hisexperiments as an exercise in zootechnics and planned tomove on to the mass reproduction of whole races ofmonstrosities (Dareste C,5 p 42).

TERATOPARTHENOGENESISDISCOVERINGEMBRYONIC STEM CELLSMost accounts of the history of stem cell research tell us thatembryonic stem (ES) cells were first discovered, or ratherisolated and characterised in 1981. But the history of ES cellscan be traced back two decades earlier to studies onteratogenesis (the production of embryonal tumours) in mice.Embryonic stem cells were first identified by the scientistLeroy Stevens in the course of his investigations intoteratomas and related cancers called teratocarcinomas. Onthis point see Lewis R, Shostak S, and Stevens LC.17 18 19

From the very beginning, then, definitions of ES cells havebeen inextricably entangled with the monstrous properties ofteratomas, teratocarcinomas and parthenogenetic growth.The question of their precise relationship to immortal,

cancerous cells has recently returned to the fore of scientificdebate.Embryonal tumours are cancers which develop without

any alteration in the cells genetic material. Tumours of thiskind usually occur in the ovary or the testis and are derivedfrom the germ cells. The more common ovarian teratomaresults from a process of spontaneous parthenogenesis, inwhich the egg is activated to growth without fertilisation, butcannot lead to a live birth. Such tumours can be benign ormalignant. In their non-malignant form, they are known asmature teratomas and are characterised by limited growthand disorganised but highly differentiated tissue:

The result is a bizarre growth known as a teratoma: adisorganised mass of cells containing many varieties ofdifferentiated tissueskin, bone, glandular epithelium,and so onmixed with undifferentiated stem cells thatcontinue to divide and generate yet more of thesedifferentiated tissues.20

The case referred to here is an ovarian parthenogenetictumour. More rarely, teratomas can be found at the base ofthe spine in newborn babies. Similar tumours can originatein adult males, too, from the germ cells in the testis.These truly bizarre parthenogenetic growths have been

found to contain sebum, clumps of matted hair, protrudinglumps of bone, cartilage, bronchial and gastro-intestinalepithelium and even teeth (a recently reported specimen wasfound to contain eight well formed teeth set in a jawlike bonestructure).21

In their malignant form, on the other hand, these tumoursare known as immature teratomas or teratocarcinomas andare characterised by undifferentiated cells with an unlimitedcapacity for growth. Although they rarely metastasise orinfiltrate surrounding tissue, these tumours grow very rapidlyand will continue to grow until they kill their host throughemaciation. Despite their differences, it is possible to derive ateratocarcinoma from a teratoma by continuously transplant-ing samples of the tumour cells from one host to another.Teratocarcinomas can be established as permanent cell lines(embryonal carcinoma [EC] cell or ECC lines) and induced toproliferate indefinitely, without differentiating. Whenexposed to certain agents, however, they can be provokedinto differentiation and, like the teratoma, produce adisorganised conglomerate of apparently normal specialisedcell types.Leroy Stevens decisive contribution to the field of ES cell

research was to show that teratomas were intrinsicallyrelated to processes of early embryonic growth. He was thusable to demonstrate that these tumours not only occurspontaneously in the germ cell, but can also be induced in theadult body by grafting the inner cell mass of early embryosinto the testes of adult mice. These experimentally producedgrowths behaved just like spontaneous teratomas, differen-tiating into a disorganised mass of multiple tissues. Suchresults suggested that teratomas could be understood as aneffect of the deregulation of the normal limits to growthrather than an inherent mutationa morphological ratherthan a genetic disorder. Commenting on this experiment,B Alberts et al comment that separating the cells from theirnormal companions deprives them of cues that wouldordinarily limit their proliferation and promote their pro-gressive differentiation. Conversely, the authors note thatthe deregulated growth of both ES cells and EC cells appearsto be reversible if the cells are resituated in a normaldevelopmental environment. (Alberts B, et al,20 pp 8978).It is to this experiment that we owe the first identification

of ES cells. Having transplanted the inner cell mass into adult




tissue, Stevens noted that some of the early embryo cellsgave rise to teratomas; the induced growths looked andacted like spontaneous teratomas, yielding embryoid bodieswhen transplanted into mouse bellies and displaying animpressive range of tissue types. These cells could also beinduced to grow as permanent, undifferentiated cell lines,just like the teratocarcinoma. Stevens named these cellspluripotent embryonic stem cells (Lewis R,17 p 2). ES stemcells, in other words, were discovered as experimental counterparts ofthe teratocarcinomamonstrosities, according to the language ofnineteenth century biology (Shostak S,18 p 182).Indeed when ES cells were first discovered, their sole

interest was thought to lie in the field of research into cancerand cell differentiation.The idea of exploring their therapeutic possibilities

emerged much later, following successful experiments usingadult stem cells for bone marrow transplants (Shostak S,18

pp 1812). It was only then that the properties of the ES cellwere rediscovered as being essentially benign and therebydistinguishable from those of EC stem cells, although theprecise nature of this difference is yet to be defined with anycertainty, as I will later show.Two events mark the emergence of the field of embryonic

stem cell research as we now understand it: the isolation ofthe first stable, long term cultures of embryonic stem cellsfrom mouse embryos in 1981, and from human embryos in1998.2224 It was these normal embryo derived cells thatbecame commonly known as embryonic stem cells.Returning to Leroy Stevens early work, I am struck by the

fact that stem cell research, with its historical connection tostudies on teratomas, appears to have followed up preciselythe line of inquiry suggested by Isidore Geoffroy Saint-Hilaire. In his passionate reflections on the parasiticmonstrosity, Isidore predicted that the study of teratomaswould provide invaluable insights into the processes ofmaterial organisation and illuminate the nexus betweenembryological and monstrous growth:

I suspect that one day physiologists will pursue the study ofamorphous monsters with an ardour equal to theindifference that almost all have shown up until recently,and that science will here discover perhaps unhoped forillumination on the mysteries of the first moments offormation of the animal. But these advances are still farfrom us: laborious research, abetted by favourablecircumstances, is necessary in order to carry them out. Inthe present state of science, we are lucky if we possess afew precise descriptions, a few exact figures of parasiticmonsters, and their scientific interest has even been so littlefelt that observers have almost always neglected topreserve those that chance has offered them (GeoffroySaint-Hilaire I,2 pp 5389).

Isidore Saint-Hilaire recognised the extreme importance ofthe parasitic monster for any future investigations intoembryology, but was powerless to reproduce them experi-mentally in his still largely tentative forays into teratogeny.Dareste, whose systematic teratogenic experiments weremore successful, dismissed the parasitic monster as anunverifiable, and perhaps non-existent, conceptual artefact.(Dareste C,5 p 230). When Leroy Stevens returned to theteratoma, according it all the importance that Geoffroy Saint-Hilaire had foreseen, he not only studied its spontaneousoccurrence in mice but also developed a subtle experimentalprotocol for provoking it into growth. In his ambition to leadorganisation along anomalous paths of development,Geoffroy Saint-Hilaire was vindicatedthe applied scienceof teratogeny had succeeded in reproducing that extreme case

of the anomalous which Geoffroy Saint-Hilaire classified as aparasitic monster.Recent work on teratomas has, however, discovered

aspects of the parasitic monstrosity which remained obscureto Geoffroy Saint-Hilaire: its relationship to parthenogenesis(explicitly denied by Geoffroy Saint-Hilaire) and to cancer(implicit in its renaming as a teratoma or monster tumour).Stevens work on teratomas combines Geoffroy Saint-Hilaires intuitive insight into the connection betweenparasitic monsters and embryological development withlater experiments on induced parthenogenetic growth. Mostfamous among these are Jacques Loebs successful attempts,in 1900, to activate the parthenogenetic growth of unferti-lised sea urchin and frog eggs by pricking them with a needleor altering the concentration of salt in sea water.The nexus between these three aspects of stem cell

researchparthenogenesis, cancer, and embryologycon-tinues to inform recent developments in the field. A numberof different techniques have been employed in the experi-mental production of ES cells. The first stable, long termcultures of embryonic stem cells were derived from mouseand human embryonic tissue in 1981 and 1998 respectively.Another line of research has sought to produce immunecompatible ES cells by creating cloned embryos from thecombination of an enucleated egg and an adult somatic cellof the prospective patient (a technique known as somaticcell nuclear transfer). More recently, however, researchhas returned to the connection between stem cells andparthenogenesis. In 2002, scientists based in the US provokedmonkey egg cells into dividing without fertilisation, usingchemical signals similar to the ones involved in fertilisationby sperm. Although experimental parthenogenesis is routi-nely carried out with laboratory mice, this was the first suchexperiment to successively induce asexual development in aprimate. In such experiments, the cells of the unfertilised egggrow up until the blastocyst stage, but are unable to developbeyond this into a fetus. These cells, known as parthenotes,are essentially genetic clones of the unfertilised egg, and yetas clones they are unable to develop into a morphologicalreproduction of their mother. When the cells of theunfertilised egg reached the blastocyst stage, scientistsharvested the inner cell mass, deriving stem cells which theythen provoked to differentiate into numerous cell typesincluding brain, heart, nerve, and smooth muscle cells.25

ON GROWTH, DIFFERENTIATION, AND LIMITSIn its ambiguous proximity to cancer, the ES cell unsettlesthe received scientific distinction between the normal and thepathological. Cancer, after all, is commonly defined in purelynegative terms as a deregulation of the normal limits tocellular growth, differentiation and division:

Creating and maintaining tissue organisation requiresstrict controls on cell division, differentiation, and growth.In cancer, cells escape from these normal controls andproceed along a path of uncontrolled growth andmigration that can kill the organism.26

Ignoring the normal limits to growth, most cancerous cellsare characterised by excessive multiplication through con-tinual self division and relative lack of differentiation, andwhen malignant, by the ability to metastasise or infiltratesurrounding tissues and spread to distant sites of the body.Most cancers arise from a mutation in a single cell whichproceeds to reproduce itself through uncontrolled selfdivision (in this sense they are said to have a monoclonalorigin).

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In textbook introductions, the deregulated growth ofcancer is defined against a number of assumptions concern-ing the limits to normal cellular growth, differentiation, anddivision. In general terms, processes of cellular growth areconceived of as a progressive restriction of potency:

A common notion that has prevailed in developmentalbiology for many years is one of cell differentiation duringembryogenesis proceeding through a series of successivebinary decisions by which cells adopt alternative pheno-types. Thus embryogenesis is commonly seen in terms ofcells following branching pathways of differentiation. Thebranching pathways are seen as representing successivecommitment of cells progressively to restricted options ofeventual cell fate (Andrews P,27 p 8).

Development, it is assumed, is an irreversible processleading from the undifferentiated and totipotent cells of theearly embryo (capable of giving rise to all the germ andsomatic cells of an organism), through a progressive andirreversible restriction of cellular fate, committing cells tomutually exclusive paths of differentiation. In the course ofdevelopment, the cells of some tissues undergo terminaldifferentiation, culminating in cell death and the finalcessation of cell division. In other tissues, old cells arecontinually lost and replaced by new ones, through thedivision of undifferentiated, progenitor or adult stem cells,cells which are capable both of continually renewingthemselves and differentiating into specific daughter cells.Haematopoietic stem cells, precursor cells in the liver, andneural stem cellsfor example, continue to regeneratespecific cell tissue throughout life. In normal growth, it isassumed, the relationship between cellular division anddifferentiation is maintained within strict regulative limits,preventing either one from predominating over the other.Whereas cell division tends towards the extreme of limitless,but undifferentiated growth, cell differentiation is associatedwith a progressive restriction of function, leading to terminaldifferentiation and a complete cessation of cell division.Normal growth itself is envisaged as a precarious balancingact between these two tendencies. As one recent overviewputs it, adult stem cells tread a fine line between death(terminal cell differentiation) and immortality (unlimited,undifferentiated division).28

According to recent definitions, it is this fine linebetween differentiation and (undifferentiated) divisionwhich is disturbed in cancer. In most forms of cancer, thecell is afflicted with a persistent and pathological non-differentiation. There are no limits to its proliferation, itwould seem, because it refuses to commit itself to adetermined, irreversible path of differentiation. Hence mostcancers arise from (stem) cells undergoing continuousdivision. The most frequent forms of cancer are those of theepithelia (epidermis and lining of the gut), tissues that areconstantly being renewed by division and differentiation ofstem cells. In normal epithelia, cells generated by stem cellscontinue to divide for a little time until they undergodifferentiation, when they stop dividing. By contrast,cancerous epithelial cells continue to divide, although notnecessarily more rapidly, and usually fail to differentiate(Wolpert, et al,26 p 429). Leukaemias, cancers of the whiteblood cells, are likewise characterised by the failure ofresident stem cells to differentiate, while dividing. All bloodcells are continually renewed from a pluripotent stem cell inthe bone marrow, by a process in which steps in differentia-tion are interspersed with phases of cell proliferation. Thepathway eventually culminates in terminal cell differentia-tion and a complete cessation of cell division. Several types of

leukaemia are caused by cells continuing to proliferateinstead of differentiating (Wolpert, et al,26 p 429).The equation between undifferentiated growth, disorga-

nised differentiation and the pathological continues toinform the most recent textbook introductions to cancer.But are these properties inherently pathological or malig-nant? The isolation and identification of ES cells has raisedsome provocative questions in relation to the concept of thepathological. Early studies defined teratocarcinomas derivedfrom teratomas as malignant growths and set out theirproperties as follows:

The most important characteristics of embryonal carci-noma cells in teratocarcinomas are their immaturity,pluripotentiality, and capacity to proliferate in theundifferentiated form, at the same time to give rise tosomatic tissues.29

It is in almost identical terms that recent textbooks definethe properties of the ES cell derived from the isolated cells ofan early embryo:

human embryonic stem (ES) cellsthat is, cells obtainedfrom the inner cell mass (ICM) of embryos at the blastocyststage and cultured in vitro. Under suitable conditions,human ES cells can divide indefinitely and give rise to awide range of differentiated cells.30

According to this definition, ES cells are characterised by acapacity for indefinite self division (potential immortalisa-tion) which they retain even when they can be provoked intogenerating differentiated cellsa capacity, in other words,for excessive multiplication which might otherwise beassociated with the pathological. Certainly nineteenth cen-tury theories of biological equilibrium would have classifiedthe ES cell as a form of monstrous growth; and in the earlyhistory of twentieth century stem cell research, ES cells wereequated with the immortal and therefore pathological celllines of the teratocarcinomas. On the conceptual confusionbetween ES and EC cells, the specialist Peter Andrews writes:

The recognition that EC cells are the malignant counter-parts of embryonic ICM cells eventually resulted in theexperiments of Evans & Kaufman (1981) and Martin(1981), who showed that it is possible to derive permanentlines of cells directly from mouse blastocysts, which closelyresemble the EC cells derived from teratomas. They termedthese cells embryonal stem (ES) cells. The normal cells towhich these lines are thought to be equivalent, namely thecells of the late ICM [inner cell mass], do not normallypersist for any great length of time. The apparent ability ofES cells to grow indefinitely and exhibit an immortalcharacteristicthat is, to present classical stem cellfeatures, seems to be a consequence of their removalfrom the embryo and maintenance in tissue culture.27

So should we define ES cells as normal or pathological,benign or malignant?In the words of one recent textbook, ES cell lines derived

from an early embryo are almost indistinguishable fromteratocarcinoma derived cell lines produced from teratomas(Alberts B, et al,20 p 896). (There is, however, an obviousgenetic difference between cells derived from a teratoma andES cells isolated from an early embryo, since the teratoma isconceived parthogenetically. This difference is annulled inmore recent directions in stem cell research which areattempting to produce ES cells for therapeutic purposes by




provoking parthenogenesis. See below.) In culture, both arecapable of unlimited self division and under certain condi-tions, pluripotent differentiation. If retransplanted into anembryo, on the other hand, both lose their power ofunlimited self division and participate unobtrusively in thenormal process of embryogenesis.In light of these confusing exchanges between normal and

cancerous cells, what remains as a definition of ES cells issimply their propensity to grow outside the limits ofregulated growth and differentiation, as defined by celltheory since the nineteenth century. The isolation of ES cellshas called into question established scientific notions ofcellular fate, potency, and determination. In the normalcourse of human embryogenesis, the totipotency of earlyembryonic cells is already restricted after the eight cell stage.When isolated from their habitual conditions of growth,however, the same cells acquire a potency which is no longersubject to the rule of progressive, restrictive determinationand therefore retain the capacity for unlimited division andpluripotent differentiation. These experiments suggest thatthe potency of a cell (limited or unlimited) is a function ofthe collective regulatory networks in which it participatesrather than an innate property. The capacity for unlimiteddivision which characterises ES cells is not, it would seem,inherently pathological. Rather, as one astute early commen-tator pointed out, the ES cell forces us to interrogate our verynotions of the normal and the pathological, the benign, andthe malignant:

Differentiation in teratomas is comparable to the normalprocess in the intact embryo. This all has led to thequestion: are the embryonal carcinoma cells reallymalignant or is a teratocarcinoma a malignant tumouronly because it contains undifferentiated, otherwisenormal embryonic cells? Finally, can one draw thedemarcation line between the normal embryonic cellsand the stem cells of teratocarcinomas?

The answer to this question is not possible, because thecommonly used concepts and criteria do not apply to thistumour model.

Teratocarcinomas are malignant not because of dediffer-entiation of somatic cells but because the differentiation oftheir stem cells does not occur and they retain theundifferentiated form. This by itself of course, does notimply that these undifferentiated cells are malignantcells. Malignancy is a most useful clinical designation, butin experimental tumour research, the differences betweennormal and malignant cells are not always so evident thata sharp distinction should be always warranted.

Several biological methods were proposed to differentiatethe malignant from benign cells. Some of them wereapplied to the study of teratocarcinoma, but the conclu-sions drawn from such experiments are not unequivocal(Damjanov I, et al,29 p 115).

In ES cells, biologists seem to have discovered cells whichare equally available to normal and pathological possibilitiesof growth. Depending on the context of their growth, stemcells can be associated with the earliest stages of embryogen-esis, the limited regenerative capacities of adult tissues, andthe pathological properties of cancer. (The behaviouralproximity between ES cells and teratocarcinomas remains asubject of debate in stem cell research. Recent studies have

established a molecular link between cancer cells and EScells, even when the latter have been derived from thenormal early embryo. The very powers of regenerationwhich stem cell research is seeking to harness bring withthem an as yet undefined risk of cancer.) Their capacity forunlimited, undifferentiated growth and disorganised differ-entiationup until recently associated exclusively with thepathological or the monstrous, to use the language ofnineteenth century biologyis here being rediscovered asa kind of protolife, the source and condition of all growth,whether normal or pathological, benign or malignant.

LIFE ITSELFIn a recent work, the philosopher and historian of science,Remy Lestienne remarks that in the last instance we tend todefine life in relation to death. Our most common, intuitiveconceptions of biological life assume that there is no lifewithout mortality, that ultimate limit to growth. And yet thisassumption is far from being scientifically established:

It is not absolutely certain that death is the inevitableoutcome of life. Some simple beings, such as seaanemones, do not seem to grow old and enjoy a longevityapparently limited only by accident. The record forobserved agelessness belongs to the colony of seaanemones harvested in 1862 by Anne Nelson for theaquarium of the University of Edinburgh and preservedunder constant surveillance, without change or apparentaging, for more than eighty years. The sea anemoneswere abandoned and accidentally perished during WorldWar II.31

In what sense is biological life defined by its relation todeath? It is no accident, I would suggest, that this question isreturning to the fore in the context of recent developments inthe life sciences. Late nineteenth century biology establishedthat unicellular life forms are immortal through self division.The life of bacteria and unicellular organisms can only beterminated from the outside, when they are devoured ordemolished by parasites. Multicellular life forms, on the otherhand, are doomed to senescencea process of aging which isintegral to the very organisation of their cells. And yet thereare exceptions to the rule. The multicellular freshwater polyp,Hydra, is capable of indefinite self regeneration through aprocess of cloning. The ES cells and cancer cells of metazoansare capable of seemingly unlimited division in culture.Canguilhem, writing on normative nineteenth century

conceptions of life, such as those developed by Bichat,Bernard, and Comte, tells us that the properly organic notionof life is fundamentally associated with limitslimits tomorphological form, the relative limit of metabolic equili-brium which distinguishes health from illness, sexualdifferentiation as a condition of sexual reproduction, and asa consequence, that ultimate limit to growth, individualmortality (Canguilhem G,8 p 172).In the atmosphere of feverish and uncertain experimenta-

tion of the late eighteenth century, these limits were not yetso indelibly established. In particular, the epigenetists(natural scientists in the Aristotelian tradition) were fasci-nated with modes of life which would later be consideredmarginalnematodes that can survive for years in a state ofsuspended animation, without metabolism, before returningto life; the immortal Hydra, and aphids which in certainseasons reproduce through parthenogenesis. Not surpris-ingly, the epigenetists were responsible for the scientifictreatises on monstrosity which would later be developed bythe nineteenth century teratologists, including Etienne andIsidore Geoffroy Saint-Hilaire.

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In the parasitic monstrosities, Isidore Geoffroy Saint-Hilaire discovered an obscure zone where life could no longerbe defined in its essential relation to limits, a latent lifethat continued to grow while remaining perpetually embryo-nic, a life that would never be born but appeared capable inprinciple of outsurviving its mother. The morphological formof these monstrosities was indeterminable. In cases wherethey seemed capable of indefinite growth (here GeoffroySaint-Hilaire appears to have been referring to malignantteratomas), their death could only come as it were from theoutside, as an accident.More recent studies on teratomas and teratocarcinomas

provide a more exact formulation of Geoffroy Saint-Hilairesintuitive insights into the nature of anomalous growth.Teratogenesis indeed calls into question the rules ofcellular differentiation and growth which twentieth centurybiology inherited from nineteenth century theories of the cell.The growth of the teratoma is not organic, in the normativesense of the termthe differentiation of functions andorgans is not orchestrated by an implicit form, a teleologicalend which would constrain the multiplication of differenceswithin precise limits and rules of non-contradiction. Theteratocarcinoma remains undifferentiated but ignores thetemporal limit to generation. In culture, it appears capable ofunlimited self division. Like cancer, it is immortal (in thesense that its death does not come from within, but can onlyintrude from the outside, as an accident). Moreover,teratomas and teratocarcinomas pose a challenge to theultimate principle of non-contradiction underlying all nor-mative conceptions of organic life in the nineteenthcenturysexual difference as a condition of organic repro-duction. As Geoffroy Saint-Hilaire insisted, the teratoma isindeed the product of a genuine conception. But this is a birthwithout fertilisation, conception as parthenogenesisthemultiplication of life from one reproductive cell. The growthof the teratoma enacts a kind of autogestation, thereproduction of the self as a clone. But while the teratomais a genetic clone of the egg cell, its disorganised growth in noway respects the rules of morphological self reproduction.Like the monoclonal cancer which proceeds to reproduce thesomatic cell through a process of delirious and fatal selfmultiplication, the teratoma threatens to engulf the body inits own embryogenesis.

Teratomas, being cancers of the germ cell (the egg or thesperm), mimic the beginning of life with apparentlyauthentic authority. Egg cell division, after all, is theoriginal story of life. The Adam and Eve of contempor-ary biological discourse, the egg and the sperm are thespecialised cells which need each other to be complete. Butthe teratoma goes it alone. Too impatient to wait for thecorrect pairing of opposites (the natural union of the twosexes), cell division in this case begins not the process ofcreation but that of potential destruction. The unfertilisedegg divides and tries to compensate for the lack of themasculine counterpart. But such parthenogenetic assump-tions can only lead to trouble. This deviant fetus threatensthe mothers body by destroying its internal social order(Stacey J,32 pp 912).

What is exceptional about recent developments in stem cellresearch is the fact that such monstrous possibilities arebeing exploited as a source of regenerative tissue. It is envisagedthat the enormous potential of stem cells to proliferate andgenerate differentiated cell types might be harnessed toproduce specific kinds of tissue on demand. The very traitsthat define teratogenesis as pathologicaldisorganisedgrowth and differentiation in the case of the teratoma, the

unlimited proliferation of the teratocarcinomaare hererediscovered as benign, even regenerative, possibilities.Here, I think, lies a fundamental shift in our understandingof health and medicine. For the science of regenerativemedicine, health can no longer be identified with theequilibrium of the self regulating organism, but comes tobe associated with the bodys capacity for cumulative,proliferative growth in far from equilibrium conditions.Health has become excessive rather than homeostatic. Atthe same time, stem cell research calls into question thedifference between the regeneration and reproduction of thebody, between regenerative and reproductive medicine. Theprocess of tissue regeneration is reconceived as an act ofpermanent autogestation, an embryogenesis which can be re-enacted throughout life.In the process, the deregulated growth of the monstrosity,

that ultimate countervalue to normative theories of organiclife, comes to represent the most extreme potentiality of lifeitself.

ACKNOWLEDGEMENTSI would like to thank the reviewers of this article for their commentsand suggestions and for pushing me to delve deeper into the complexhistory of stem cell research. I would also like to thank ProfessorPeter W Andrews from the Department of Biomedical Science,University of Sheffield, for providing me with detailed informationon the connection between teratoma research and stem cells and DrWendy Chee, pathologist at Prince Alfred Hospital, Sydney, forclarification on cancer and teratomas. Lastly, I would like toacknowledge the inspiration provided by Jackie Staceys work,Teratologies: a Cultural Study of Cancer.

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science of monstrosityRegenerative medicine: stem cells and the

M Cooper

doi: 10.1136/jmh.2003.0001372004 30: 12-22 Med Humanities

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