Searching for Information Próximo Milênio E Epidemiologia: Em Busca

ARTIGO ARTICLE 765

The next millennium and epidemiology: searching for information

Próximo milênio e epidemiologia: em busca da informação

Luis David Castiel 1

1 Departamento de Abstract On the eve of the new millennium, it has become ‘natural’ to admit the emergence of Epidemiologia e Métodos tendencies to perform evaluations and inventories of the past and attempts to forecast future Quantitativos em Saúde. Escola Nacional scenarios. While recognizing the ensuing uncertainties, the current paper takes this point of view de Saúde Pública, as the point of departure for proposing a discussion on the future directions and prospects of Fundação Oswaldo Cruz. epidemiology. Based on the pertinent analyses performed by the Sussers (father and son), I ap- Rua Leopoldo Bulhões 1480, sala 828, Rio de Janeiro, RJ proach and discuss the scope and limits of new aspects assumed by the field, especially to the ex- 21041-210, Brasil. tent that it has included techniques and instruments from bioinformatics and molecular biolo- [email protected]. gy. In the latter areas (amongst many others), the notion of information has gained enormous fiocruz.br importance. I then proceed to analyze the conceptual origins and shifts in this notion, in addition to possible repercussions and effects on the field of biological sciences in general and their research practices in particular. Key words Epidemiology; Molecular Biology; Information

Resumo Diante da expectativa de um novo milênio, torna-se “natural” admitir o surgimento de inclinações para procederem-se a avaliações e balanços do passado e a tentativas de prever-se cenários futuros. Este texto parte deste ponto de vista – reconhecendo suas incertezas – para pro- por uma discussão dos rumos e perspectivas da epidemiologia. A partir das análises nesta di- reção pelos Sussers (pai e filho), são abordadas e discutidas o alcance e os limites de novos aspec- tos assumidos pela disciplina, especialmente, ao incluir técnicas e instrumentos da bioinfor- mática e da biologia molecular. Nestas áreas (entre muitas outras), é notável o fato da noção de informação possuir enorme importância. São, então, analisadas origens e deslocamentos con- ceituais desta noção e possíveis repercussões e efeitos no campo das ciências biológicas, em geral, e de suas práticas de pesquisa, em particular. Palavras-chave Epidemiologia; Biologia Molecular; Informação

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“We learn to build discourses on reality that are chronological time is usually seen as a move- highly abstract, but which we know how to rec- ment, allowing for two cases: ognize as true or false. It is a generalization, a 1) time as the movement of objects in con- fantastic extrapolation of our immediate expe- tinuous, linear fashion, with the future moving rience with error or lie. In fact, this is a concrete, in our direction and the past being left behind. unique experience by which we learn simulta- 2) time as movement across a landscape. In neously and concurrently a unique thing and a this case, time can also be seen as “stopped”, discourse on this thing that is different from while we are the ones that move through it what we learned about it.” (e.g., “we are getting to the end of the year, or Henri Atlan close to Christmas”). In a word, the metaphorical structure presents “time” passing us from front to back, whether we are standing still and Introduction: turn-of-the-century, “it” is moving towards us or we are moving to- inventories and forecasts wards it, while “it” remains static. That is, something or someone must be moving... There is no It is known that “ends of periods” exercise curi- other way, since as the poet once said, “Time ous effects on human beings. They may be never stops.” weekends (here, specifically, there is an obvi- According to Lakoff (1992), such descrip- ous, strong link to leisure, by opposition to so- tions of time in terms of movement, objects, called “workdays”), ends of the month (pay- and places have a biological basis, since our checks and bills...), ends of the year, decades, sight specifically detects these phenomena, quinquecentennials (a fascination with num- while we have no specific sensors for the pas- bers ending in fives and zeros), turns of cen- sage of time. In order to perceive time, we must turies, and so on... When such periods end, we use references obtained from our available vi- join in acts of celebration, joint remembrance sual sensors. Yet we are unaware of this in our (co-memmoration), weddings, birthdays, quin- daily lives. In fact, this does not even matter in quecentennials, centennials (of births and solving everyday problems (and it may be more deaths of both persons and human creations)... convenient to ignore it). As Lakoff & Johnson An “end of period” is obviously an arbitrary, say: conventional temporal category (human groups “(...) All this detailed and consistent culturally define the ways by which they mark metaphorical structure is part of our daily lit- the passage of time) created by these peculiar eral language for time, so familiar that we nor- beings that produce things which recursively mally do not realize that it is a metaphorical affect them in what is often an unpredictable construction” (Lakoff & Johnson, 1980:82). way. Regardless of the metaphorical configura- In the face of presumed “chronological ter- tion of time that comes into play, this prelimi- minations”, there emerges the task of produc- nary comment requires identifying the “topo- ing evaluations, inventories, and value judg- graphical” perspective adopted by this com- ments. To what ends? In very simplified terms, mentator, situated as I am below the Equator, several can be identified: with all the possible sins this may entail, espe- a) more explicit ends: to monitor and ob- cially the geographical and sociocultural gaps jectively identify trajectories and processes un- (with unavoidable biases and prejudices) vis-à- der way over the course of a given period of vis the players in the Anglo-Saxon scenario, time; where most epidemiological work and futuris- b) less explicit ends: to (re)describe for our- tic speculation is produced. I refer to this line selves (by redescribing to ourselves) “what of work because of its undeniable influence on happened” in terms of ordered narratives, full the field of epidemiology worldwide. Sooner or of symbolic components, seeking meanings in later we feel the repercussions of what happens the “subjective” happenings that accompany in epidemiology above the Equator. the events of chronological time. Although such a speculative undertaking There appears to be a particular need to might spark criticism due to the risk of a mis- prepare for the vicissitudes of the “fate” that taken reading, I should highlight the perti- “awaits us”... We need periodic structures to al- nence of such an exercise, since it creates pos- low for the ordered narratives of our (re)de- sibilities for reflection and perhaps organiza- scriptions of ourselves and our surroundings. tion vis-à-vis overwhelming and adverse situ- A brief comment is in order on our metaphor- ations (after all, there are always “priorities” ical constructions with regard to the notion of defined according to the respective interest passing of time. In this sense, the passing of groups involved). This paper thus discusses an

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outline for epidemiology “in the next millenni- by sociocultural practices in contemporary so- um”. In other words, my goal is to call attention cieties, along the lines previously hinted at by to the description of future scenarios (even ad- the genre known as “science fiction”. mitting the decline of futurology, a discipline in vogue in the 1970s) in order to orient what could (or should) be “the best” (insofar as pos- Predicting the future: sible) prospects for Sub-Equatorial epidemi- a jigsaw puzzle without all the pieces ology. While there is an underlying “evaluative When we were kids, we used to have fun play- furor” in this exercise, justified by the spirit of ing with kaleidoscopes, which would assume expectation surrounding this period of “new various abstract shapes, with symmetrical times”, on the other hand it is necessary to planes [kali- comes from the Greek kállos, or adopt a certain degree of complacency based “beautiful” (hence calligraphy) (Ferreira, 1986)]. on the obvious reasons for the fallibility of any The designs changed their appearance based current forecast: in addition to the usual “ob- on the mechanical movement of the object, servation biases”, there is also a great lack of maintaining the same elements, through a play precision resulting from the instability and on mirrors. We could control the speed of the rapid pace of today’s technoscientific and so- changes and even carefully stop the toy and ciocultural changes. show the resulting designs to our friends. Outside the walls of academe, astrologers, Along the lines of this playful metaphor, the “wizards”, “prophets”, “soothsayers”, and various new “kaleidoscopes” are built with electronic crystal-ball “experts” are in great demand. Espe- microcircuits linked to screens (LCDs or tradi- cially (et pour cause?) at a moment when the tional videos or kinescopes) and/or internet natural sciences in general have begun to view networks, with extensively multiplied elements most of the systems surrounding us as complex that shift cinematically, whereby the images and dynamic, thus highlighting their stochastic can be animated, in script form, and anthropo- character and resulting unpredictability (in de- morphic, allowing for control (or so-called “in- terministic terms). Worse yet, some researchers teractivity”) with objectives, phases, or (for at “state-of-the-art” research centers, like the those who so desire) heavy doses of competi- Santa Fé Institute in the United States, have be- tion and scoring (videogames) or even “hu- gun to doubt the possibility of reaching a uni- manoid” demands (see Tamagotchi, the egg- fied theory for complex systems. According to watch, and equivalents). them, on the one hand there may be excesses Although it may be a truism, it is important and distortions in the so-called “scientific jour- to stress that our observations are a procedure nalism” with regard to such ideas as entropy, that seeks to demarcate some intelligibility in a chance, chaos, and information, amongst oth- hypercomplex, intertwined, and simultaneous ers. On the other, the problems start with the picture. Very well, in these times marked by the lack of precision in the concept of “complexi- proliferation of “new kaleidoscopes”, mixing ty”. More than 31 definitions for this term have the playful and figurative senses (the rapid and appeared already, to the point where the idea changing succession of impressions and sensa- has lost its meaning, and at least one author tions), our goal is to ascribe possible meanings has bemoaned that we are moving from com- to the new “figures” that are shown to us, view- plexity to perplexity (Horgan, 1995). Whether ing them initially as mysteries, like another toy, such issues are pertinent or not, in everyday the puzzle, which also serves to designate an terms they undermine belief in the redeeming “enigma” or “perplexity”. The point is that we ability of science to mitigate human suffering feel not only delight with the images produced and respond to the anxiety identified above in by the neo-kaleidoscopes. We are both ob- the (re)descriptions of both ourselves and what sessed and bewildered by such dazzling virtual is going on around us, in the face of the un- aesthetics. ceasing proliferation, multiplicity, and simul- Because of our bewilderment with the taneity of events... speed and proliferation of new enigmas (and Before moving on I should touch on two their “puzzling effects”), we are in constant points. First, the “next millennium”, or rather need of producing new “solutions”, i.e., new its “spirit”, is already amongst us... In fact, it has meanings (albeit transient, fragile, and local). been said that the future began some time ago. Thus, while our “game” is now a kaleidoscopic Examples abound in other fields of knowledge, mix of puzzles and enigmas, we must admit in sectors of (bio)technological production, that we have no definitive solution, model, or and in the “futuramic” characteristics assumed gold standard. There are pieces missing from

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the puzzle. Meanwhile, other pieces are con- hand, there is “traditional” epidemiology (the stantly being added that provide multiple, author uses the term in a favorable light) whose complex “configurations”, depending on the “motivation” is public health and its ideals – observer’s point of view. Thus, more than ever promotion, prevention, and the control of in- before, faced with the unpredictability of con- juries to health, through structural epistemo- temporaneity, predicting the future has in- logical strategies with a realist focus and popu- creasingly become an exercise in providing a lation studies and interventions in a historical feasible order for the present. Such predictive and cultural context, using observational re- exercises should be viewed in this light. search techniques. On the other hand, there is “modern” epidemiology, whose “motivation” is scientific/ Describing the “epidemiological academic, with a predominantly biomedical situation” view using reductionist epistemological strategies of a positivist bent, studies and interven- Petersen & Lupton (1996) produced a critical tions at the individual level (in organs, tissues, text with brilliant arguments on the results of cells, and molecules...), with the exclusion of contributions by risk-factor epidemiology in experimental research contexts and techniques constituting the “new public health” and its (whose basic model is the randomized clinical corresponding “new morality”. While a rhetoric trial). This scheme, in addition to its poorly dis- of regulation is developed through the risk dis- guised Manicheaism, eludes several issues. In course, it is now the “irrationality” of individu- principle, it is at least debatable to affirm a als adopting harmful lifestyles that much be clear distinction between the epistemological approached through the rationalizing light of strategies and approaches of the various water- epidemiology. The authors emphasize the cen- sheds. Furthermore, as analyzed by Ayres tral role of statistical and epidemiological quan- (1994), public health underwent a decisive re- tification in the construction of epidemiological arrangement in terms of scientific normative- “truths”. In reality, such “facts” are presented un- ness in the United States with W.H. Frost in the der the guise of the neutrality and objectivity of 1940s and 50s, in a process that began in the scientific knowledge, without revealing the so- late 19th century. A hygienist share of the field cially defined contingencies by which epidemi- was incorporated by the state, i.e., public ological constructions are built and interpreted. health per se. Another part, in the disciplinary Furthermore, in the public communication of form of preventive medicine, was linked to findings, the indetermination and correspond- medical and health care activities, with reper- ing margin of error inherent to operating the cussions on the training of health professionals statistical/epidemiological device when referred and the shaping of corresponding biological to the individual are not usually explained clear- knowledge on the human disease process. Epi- ly, and when they are, there is no certainty as to demiology as a scientific activity took hold in the degree or reliability of understanding by medical schools together with other bioscien- the lay public receiving such information. As tific contents in medical training. That is, we discussed previously (Castiel, 1998), individu- are now experiencing the paroxysm of a split- als generally lack statistical literacy training al- ting trend that appears to have generated at lowing them to access knowledge to handle the least two epidemiologies displaying different implications of probabilistic reasoning. structures. One is “sanitary/collective”, inter- Is it still possible to speak of Epidemiology ventionist, linked to population-based prac- in the singular and with a capital “E”? That is, tices, surveillance, disease control, health edu- there is strong evidence that different epidemi- cation, etc., in a sense a subsidiary of the other, ologies have taken shape whose adjectives have “scientific/academic”, producing evidence on become “last names” [in Portuguese and other the “natural history of diseases”, in relation to languages in which adjectives follow nouns – which both public health and medicine are ex- Translator’s note], connoting different clans pected to base their actions. and sparking feuds and disputes for hegemony Under the scheme of “epidemiological to achieve capital-letter, dominant status. So as modernity” proposed by Pearce (1996) there is not to dwell too long on this topic, a summary no clear indication of the trend called “clinical of the essential differences in such watersheds epidemiology” or “evidence-based medicine”. was suggested by Pearce (1996) (slightly modi- In fact, this expression denotes a grammatical fied), and despite the limitations inherent to inversion where one notes the notion of the ab- summarization, it is sufficiently illustrative (for sorption of epidemiological contents by medi- greater detail, consult the author). On the one cine, thereby consummating a disciplinary

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shift. Clinical medicine substantiates itself, along with his son, i.e., Mervyn and Ezra Susser and the adjective is provided by the epidemio- (1996). A study divided into two papers (a pre- logical techniques which produce a suggestive- liminary version was presented at the Congress ly solid basis – evidence! of Epidemiology in Salvador in 1995) describes Barata (1996) identifies the ideological di- past epidemiological eras and proposes a fu- mensions embedded in this shift, with empha- ture picture: that of health statistics, based on sis on the positivist facet of the technobio- the miasma paradigm, in the first half of the sciences, through closely linked myths: 1) the 19th century; that of infectious diseases, with unconditional objectivity of scientific knowl- the germ theory, in the late 19th and early 20th edge and its capacity to display “truths”; 2) the centuries; and that of chronic/degenerative power of the probabilistic quantitative arsenal diseases, emphasizing the exhaustion of the in this process; 3) the notion of unlimited black box (risk factor) theory, during the latter progress in the technological development of half of the 20th century. products, techniques, and interventions aimed According to the Sussers, the field’s fu- at prevention, detection, and treatment; and 4) ture is shaped by “eco-epidemiology” (whose the strong belief in the neutrality of scientific metaphorical paradigm is that of “Chinese box- enterprise, whose main premise is the dichoto- es”), characterized by an ecological point of my between subject and object and conse- view studying “relations within and between quently the control of both, optimizing objec- localized structures organized in a hierarchy of tivity and avoiding the hazards of subjectivity. levels” (Susser & Susser, 1996:676); an analyti- Despite the trials and tribulations of the cal approach involving “[a]nalysis of determi- struggles for prestige, the situation sometimes nants and outcomes at different levels of orga- shows a picturesque side. A curiously dramatic nization: within and across contexts (using and unabashed review by Carl M. Shy (1997) in new information systems) and in depth (using the orthodox American Journal of Epidemiolo- new biomedical techniques)” (Susser & Susser, gy proceeds literally to a “judgment” of acade- 1996:676) (here, read especially recombinant mic/scientific epidemiology. The field’s alleged DNA manipulation techniques and molecular “crime” was to have devoted itself primarily to markers and probes, constituting what is al- studies whose main perspective was to “discov- ready known as “molecular epidemiology”). er” risk factors in the relations between given The preventive approach is based on “[apply- exposures in groups of individuals and their re- ing] both information and biomedical technol- spective outcomes, a conservative proposal ogy to find leverage at efficacious levels, from which, according to the prosecution witness contextual to molecular” (Susser & Susser, (the author), constituted a “failure”, since it ex- 1996:676). cluded community and ecological dimensions In other words, the Sussers appear to feel and their interrelationship with socioeconom- that a bright future for epidemiology rests pri- ic, cultural, and behavioral aspects in the un- marily on the transdisciplinary conjugation of derstanding of the individual disease process. bioinformatic techniques with so-called “mol- This explicit critical stance by authors from ecular epidemiology”. the Anglo-Saxon epidemiological community I will not dwell here on the undeniably im- towards “modern” epidemiology and the as- portant issues of interdisciplinarity in general sumption of the limitations of risk-factor ide- and its Collective Health dimensions in partic- ology is quite recent. As suggested in a previ- ular. Interested readers are referred to Almei- ous study (Castiel, 1998), it mimics certain as- da-Filho (1997) and the respective debate with pects of the so-called Latin American social other authors. Suffice it to mention the major epidemiology of the 1970s, of a Marxist strain. effort in this direction in successful studies on Could it be that the fall of the Berlin Wall in cholera, a well-known epidemic disease, con- 1989 brought greater freedom for the so-called sidered paradigmatic in the construction of left-wing intellectuals of the United States, to epidemiological science. Interdisciplinarity the point that they can now speak out without has served to propose a consistent predictive fear of a return to witch hunts? model for outbreaks of the disease, involving processes for identifying strains of the cholera vibrio using biochemical techniques (like PCR, Tracing the future of epidemiology monoclonal antibodies, and fluorescent la- beled RNA probes), in addition to epidemiolo- Let us now turn to a renowned Anglo-Saxon gy itself, oceanography, ecology, microbiology, epidemiologist originally from South Africa, marine biology, medicine, satellite image geo- now based at Columbia University in New York, processing, and (bio)informatic techniques.

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This position postulates the influence of through methodological approaches proper to the amount of chitinous marine zooplankton, epidemiology. like copepods, tiny crustaceans, elements in The necessary quantifications or measure- the food chain of fish, as hosts for the vibrio. ments are based on modern molecular biologi- The copepod population is a function of global cal laboratory techniques, aimed at the follow- climate changes (like the El Niño phenome- ing: a) direct detection of changes in molecular non, which provides rain, brings nutrients from structures (both pathogens and individuals the coastal areas, and heats the ocean), and its susceptible to disease) and b) indirect detec- movements are related to the marine winds tion using immunologic techniques to verify and currents. In addition, molecular genetic the existence of specific molecules from given probes have also shown that certain vibrio products of gene activities. The term originat- strains assume a viable and pathogenic state, ed from cancer epidemiology studies using yet refractory to culturing in the laboratory. molecular biochemical techniques in the 1980s One can thereby detect and count Vibrio choler- (McMichael, 1995). ae in environmental samples and measure the It also serves to: 1) demarcate the gradient corresponding degree of contamination (Col- of events from exposure to disease – internal well, 1996). dose, biologically effective dose, early biologi- The expression “bioinformatics” encom- cal effect, and altered function/structure, clini- passes mathematical and computer tech- cal prognostic significance; 2) identify expo- niques employed in the study of biological sures to lower or older doses to presumed nox- problems. Such techniques are used increas- ious agents; 3) reduce classification errors in ingly as powerful tools to study natural systems exposure variables for disease; 4) indicate in various branches of biology: ecology, genet- mechanisms; 5) establish the role of exposure ics, evolution, immunology, virology, and epi- to given factors in the susceptibility and vari- demiology (Levin et al., 1997). ability of individual response; and 6) expand The field incorporates non-linear and non- the verification of risk levels in individual and parametric mathematical methods and the group terms (Schulte & Perera, 1993). study of genomic sequences of pathogens (Es- Groups of studies have emerged in the cherichia and Listeria), or so-called phyloge- United States that have begun to discuss rela- netic analyses; investigation of host-agent co- tive risk/benefit issues involved in the transi- evolutionary interactions; genetic immunoepi- tion of predictive genetic tests from basic re- demiology; and modeling of immune response search to clinical practice. The benefits are evi- patterns resulting from the complex dynamics dent: screening of various diseases in neonates, involving pathogens and the immune system making early intervention possible in many with control strategies (Levin et al., 1997, op. cases. But for diseases like breast cancer, de- cit). Many new drugs have been developed us- spite the availability of predictive genetic tests, ing these techniques. There are pharmacoge- there is still no evidence that preventive mea- netic prospects for expanding the power to sures or optimum treatment are devoid of risk identify genomic characteristics of individuals, or fully effective. The risks can be summed up grouping them according to their correspond- in the issue of “predictive uncertainty” as to the ing genotypical configurations and prescribing occurrence of future disease vis-à-vis some more “personalized” and supposedly more ef- tests. This also applies to non-genetic tests fective drugs (Cohen, 1997). (Holtzman et al., 1997). In fact, this is still one In order to simplify the presentation, we of the crucial problems in risk as a probabilis- will classify issues pertaining to the mathemat- tic category for exposed individuals in clinical ical modeling of “molecularization” aspects of contexts. Physicians (and patients) generally epidemiological studies. We have discussed the feel alone at such times, with no data as to the pertinence of the expression “molecular epi- validity and utility of recently developed tests. demiology” in a previous article (Castiel, 1998), And I believe that even when there is access to but it is worthwhile to refer to its descriptive such data, decisions have not become substan- side now and then proceed to the discussion of tially safer or guaranteed. its basis in molecular biology. We should also mention the existence of a First of all, how does one define the term? “molecular” watershed in the epidemiology of Simply speaking, molecular epidemiology con- infectious/contagious diseases. The approach’s sists of the use of biological measures or mark- principles are based on the fact that bacterial ers at the molecular level in epidemiological genes coding for molecules that perform activi- research. In other words, studying the relations ties in the basic maintenance of the microorgan- between exposure and disease in populations ism’s structure and function do not undergo ma-

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jor changes over the course of evolution. On the measures. Depending on the problem, all scales other hand, other genes are under strong selec- can be important, from the individual to the tive pressure. For example: those coding for cell greater metropolitan level. The central issue is membrane proteins. Due to the common ori- the following: how does one effectively adjust gin of medically relevant bacteria, one can con- and calibrate the number of elements in the struct the respective evolutionary trees based on model to a given context? the analysis of the genes coding for the constant There are many epidemiological studies macromolecules (McDade & Anderson, 1996). approaching the dynamics of infectious dis- Sequencing of other group-specific vari- eases from the above-mentioned perspective able bacterial genes is used to type strains and (see Levin et al, 1997, op. cit). Still, in so-called identify differences between such bacteria. Al- mathematical modeling and computer simula- though it is not possible to construct an evolution techniques one must consider such com- tionary tree for all viruses, since there are no plicating factors as interactions between spa- conserved molecules as there are with bacte- tial and genetic heterogeneity, non-linearity, ria, there are conserved and variable genes al- and stochasticity. Even greater problems for lowing for the identification of relations within modeling in epidemiology are transmission viral groups. This technique is also called phy- variability according to social and geographical logenetic analysis (McDade & Anderson, 1996). space or the diversity and heterogeneity of in- Such procedures serve to: 1) study outbreaks dividuals. How and at what level can one rep- of diseases of unknown origin (e.g., hantavirus, resent spatial variations in intrinsically non- a respiratory disease with a high case-fatality linear contact processes underlying transmis- rate); 2) detection and identification of culture- sion? An example is the highly dynamic spatial resistant bacteria (e.g., Whipple’s disease, a sys- and temporal patterns in the AIDS epidemic temic disease involving arthralgia, abdominal and the possibility of chaotic, non-linear dy- pain, diarrhea, malabsorption, and wasting); 3) namics in establishing complex transmission establishment of unusual forms of disease networks (with high degrees of imprecision) transmission (e.g., AIDS and HIV-positive den- (Levin et al, 1997). tists); 4) verification of long incubation periods And we should remember that mathemati- in rabies infections (bites in immigrants having cal models can provide an unjustifiable feeling occurred in their countries of origin more than of verisimilitude. In reality they are imitations six years previously), 5) paleomicrobiology (ge- or simulations of reality that attempt to repre- ographical identification of the origins of retro- sent where dynamic or complex processes and virus strains in the case of HIV and HTLV-I) systems really occur. According to philosopher (McDade & Anderson, 1996). Naomi Oreskes of Dartmouth College, quoted Even so, it is important to highlight that in by Horgan (1995:77), “Verification and valida- the current state of the molecular arts, one tion of numerical models of natural systems is notes that exposures to presumed external car- impossible.” At best, one can obtain partial, cinogenic agents lead to the formation of DNA approximate knowledge. This is due mainly mutations in receptor tissues (adducts?). This because such models deal with “open” sys- does not necessarily mean establishing causal tems. Affirmations than can be firmly verified nexuses, since there are still elements missing (or validated) are ones dealing with “closed” at the individual level to sustain the relation- systems, in which all of the variables are taken ship between such molecular alterations and into account and amenable to monitoring cancer genesis (McMichael, 1995). In other through mathematical logic and algorithmic words, even with the vigorous evidence back- approaches. ing the determinant role of certain biomarkers Oreskes emphasizes the rhetorical power of in carcinogenesis, exceptions to associations mathematical models and their potential for viewed as causal have not been unconditional- convincing people based on the assumption of ly ruled out (Vineis & Porta, 1996). their capacity to represent “reality”. By analogy with literary works, which can have characters based on either existing or fictitious facts and Discussing the scope and limitations persons, the following crucial question arises: how much of the respective elaboration is Bioinformatics based on: 1) the observation and measurement of accessible phenomena; 2) presumably con- The greatest computational challenge in highly sistent, well-informed assessments; and/or 3) non-linear stochastic systems is the represen- convenience (Horgan, 1995)? Isabelle Stengers tation of complexity and the impact of control (1993) sees models largely as “mathematical

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fictions”. Furthermore, they constitute a new borders between what is possible, real, virtual, modality for putting fictions to the test. With and actual become fuzzy. the new perspective raised by the development The triumphant tone employed by Lévy of (bio)informatic techniques, the use of in- suggests a deification of Virtuality [whereby the creasingly powerful computer systems as sim- capital “V” becomes a “logical imposition” (!?)]. ulation tools has led to the rise of “new sophists” Indeed, along this line of reasoning, It would be in the scientific milieu. a “manifestation” of (and for) virtuality. Would Stengers (1993:153) refers to “researchers it thus be mandatory to believe that virtuality whose involvement no longer relates to a truth possesses the (omni)potence of “existing” in which lays fictions to rest, but to possibilities, order to become an act, i.e., “to happen”? De- whatever the phenomenon may be, for the riving from this elaboration is the establish- mathematical fiction that reproduces it”. The ment of processes which ineluctably constitute same author quite properly raises the ethical stages or phases of the happening which, we issue of simulation: to “what” does an investi- stress, may or may not actually happen. gation performed on virtual molecules and From the biological point of view, Lévy’s populations refer? To what extent are such reasoning would be quite applicable to bacte- studies performed exclusively on abstractions, ria reproducing by fissiparousness and occa- and what are the representational links to sionally undergoing mutations from influences “true” elements belonging to the so-called “re- in the context. But a fecundated human egg al” world. Therefore, what kind of enunciates constitutes a happening of a quite different or- can they generate? They obviously no longer der from that of an adult organism. One can constitute experimental or observational find- even conceive of them being distinct happenings. ings, albeit possessing links to each other. A In a word, what kind of data or findings are human egg appears not to possess a mind, obtained or produced by simulation studies? while an adult organism appears to possess This situation challenges the idea of truth as an one. Here, the cautious use of the verb “to ap- arrangement involving the explanation and pear” is due to our intent not to delve into ani- “reality”, a notion dear to the natural sciences. mist theological discussions. Indeed, note how Such contingencies where the notion of virtu- Lévy leads us towards such issues. ality imposes itself further subvert the organi- In a word, despite the efforts by Lévy, prob- zation and consistency of scientific disciplines lems with the relations between what is possi- and knowledge. ble, real, virtual, and actual remain, as do their Lévy (1995) proposed a scheme to deal with definitions. Since the matter is something con- this order of problems. According to him, any sistent, externally produced, objectifiable, re- event can: 1) be latent in its virtuality and exist producible, and amenable to shared descrip- as such and 2) manifest itself in its actualization (and interactivity) and is thus valid, would tion, and thus occur. In this sense, actualiza- it be absurd to conceive of the paradoxical im- tion would invent a form of happening as a age of a “true hallucination”? Perhaps the most modality of creation (Lévy, 1996). The “tempo- appropriate pathway through this state of rality of actualization”, according to Lévy things would be to assume the condition of en- (1996), “is that of processes. (...) To the extent tities with intermediate statutes, hybrids gen- that there are as many temporalities as vital erated by virtual simulations and images, mix- problems, virtualization moves in time with the tures of “reality” and “representation”, yet not times. Virtualization emerges from time to en- symmetrically shared. According to Philippe rich eternity. It is the source of times, processes, Quéau (1994), virtual images are a mixture of and histories, since it commands actualizations idol and icon, but with a predominance of the without determining them. Creator par excel- first order, as long as we understand /idol/ in lence, virtualization invents questions, prob- the sense derived from Indo-European roots, lems, devices that generate acts, process lin- i.e., that of “knowing” and /icon/ as an image eages, and machines for the future” (Lévy, 1996: that seeks to capture similitude (Quéau & 139-140). Sicard, 1994), images of reality that produce I do not feel that Lévy has solved the prob- and multiply knowledge, but no longer with a lem satisfactorily. In my opinion a brief obser- concern over defining them according to their vation suggests the risk of semantic raveling: if statute as real or virtual objects. But their ethi- the event “exists” at one level and “happens” at cal effects are certainly important in light of another, what does it mean “to exist” after all? the potential for twisting the role of image re- That is, we find ourselves in the midst of onto- production techniques as documentary proof logical issues in a strange context where the of facts...

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Molecular biology relations with the body, thought, and disease (Lesgards, 1994). We turn now to the pertinence of theoretical Although it may seem obvious, note that and epistemological contents conveyed by current biotechnological engines require deep molecular biology and whose links to molecu- and urgent reflection and investigation. In our lar epidemiology (with or without quotation case, manipulative techniques used on human marks) are obvious. This leads unavoidably to a beings are a particularly hot issue in relation to problem. How does one produce a balanced Lesgard’s topics. But what will our “bio-point description with synthesis and depth without of view” be? How do we conceive of and deal committing improprieties or neglecting essen- with life sciences today? With which analytical tial aspects of the field, especially if the point tools? Under which epistemological premises? of view of the observer-interpreter is situated Or are these questions not relevant? They are. in the epidemiological field...? For better (or But the “engineers” (genetic and otherwise) are worse), at this stage of the game, the allusion preoccupied with more “concrete” “things” – to to (more) difficulties should not prevent us efficaciously produce new (bio)technical ob- from continuing our exercise. The greatest risk jects and make them available as quickly as is to scare off any erstwhile and understanding possible. readers once and for all and perhaps to fuel the In other words, I believe we should doubt fires of our critics... that current concepts and instruments based Molecular biology (MB) emerged as a disci- on games to analyze language and symbols are pline through the fusion of chemistry and biol- consistent enough to “monitor” and under- ogy, with the creation of techniques with a lan- stand what is going on in the technobioscien- guage of their own, the object of which are bio- tific world. To accompany this milieu, I believe logical macromolecules (Atlan, 1986). There we must delve into the “biotechnicalities” and are several expressions with a juxtaposition of seek insofar as possible to accompany their aspects that are correlates of the so-called MB unceasing production, even while knowing field. Two are particularly evident: biotechnol- that we are at a disadvantage in this “race”. It is ogy and genetic engineering. Technical vigor quite difficult to carry out attempts to decode, appears in both, ruled by the criteria of pro- translate, and almost simultaneously reflect on ductivity, applicability, and efficacy. The term the multifaceted repercussions of the techno- “engineering” even derives from the notion of bioscientific field and its prolific production “engines”: skills and devices allowing one to when one is removed from the production cen- overcome opposing forces. ters and/or lacks the minimum technical train- In the technological field, more and more ing (whatever that level might be) for such an double-faced products and processes for use undertaking. by men are invented by engineers whose pow- Various editions of Science expressed the er appears in the “great river of technique, first doubts as to the reliability of the experi- which in overflowing is capable of both fecun- ment that produced Dolly. The original paper dating the adjacent plains and causing irreme- had been published in Nature. Both journals diable erosion, dragging topsoil and causing are sources of frequent consultation by health, pollution, relieving men of their burden and science, and technology columns from the lay subjecting them to new obligations, elaborat- press. Two articles in Science covered the fol- ing a contest that manufactures as many ‘win- lowing themes: ners’ as it does outcasts, developing communi- 1) Recognition of the pertinence of Carlo cations fostering improved ‘communion’ even Woese’s theory (two months after he formulat- while multiplying the number of ‘excommuni- ed it) concerning the existence of a domain of cates’” (Lesgards, 1994:11). unicellular living beings different from all oth- This sharp diagnosis by Lesgards is accom- er one-celled beings. panied by a frightening statement. The intel- This new branch, called Archaea (including lectuals who purport to dwell on “what is going the extremophiles, or beings living in extreme- on” and to produce reflections concerning the ly high or low temperatures and with great world around them have never lagged so far biotechnological potential) completely altered behind the changes produced in the vortex of the make-up of the evolutionary tree of living the prevailing technological trend, perhaps beings with its two consecrated branches, Bac- due to the fact that the simultaneously prolif- teria and Eukarya (where we are located on erative and dizzying effects have uniquely al- some branch). The point here is not to dwell on tered our ways of seeking order in the world by Woese’s methods in 1967, but to point out that subverting notions of time and space, identity, his findings have been confirmed by current

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sophisticated molecular techniques. Yet his Rare indeed are the situations that are readily study received no recognition whatsoever discernible in dichotomous terms (i.e., like when it was published in the Proceedings of the black-and-white, when the norm is usually National Academy of Sciences. Woese was con- shades of gray). As if it were possible, based on sidered an introvert. He never attended the sci- an analysis in the heat of events, to reach con- entific meetings of the microbiology societies. clusive judgments (of this magnitude) vis-à-vis Some considered him a “nut”. The point was the emergence of a field or discovery. In gener- that his article was ignored by the more presti- al, it is impossible to quickly perceive the in- gious microbiologists of the time (Morell, 1997). nocuousness (which generates the quotation Events like this are hardly uncommon. In marks) of a finding like “cold fusion”, which the field of genetics, the lack of recognition for proved to be a fluke and was relegated to the Mendel’s seminal work is infamous. Genetics past. At any rate, there is strong evidence for historians point out that his groundbreaking the relevance of functional genomics. But will study was originally published in a minor it be possible some day “to study all genes or journal. proteins at once” in human beings and mea- 2) The recent appearance of a “new” sub- sure their effects? The most sensible answer is discipline, functional genomics (FG), a pre- inconclusive: maybe... dictable field in logical terms, although still Such examples indicate the great difficul- poorly defined, but already frequently quoted ties one faces today in keeping up-to-date and in the specialized domains (Hieter & Boguski, certain of the pertinence of findings presented 1997). Very well, while the term “genome” (an in the main publications from one’s respective organism’s set of genes and chromosomes) was field, plus their intersections (not to mention coined over 75 years ago, genomics was only the countless internet sites and links...). I fear created in 1986 to define the discipline in this may be the scenario that is unfolding: the charge of mapping, sequencing, and analyzing great probability of extrapolating our capacity the genome. Genomics can now be divided in- to follow and understand the minutiae and to structural (the complete, high-resolution spin-offs of what is produced (to the point of transcription of the physical genetic maps of saturation) in our areas of interest. There is a an organism’s DNA) and functional (the appli- plethora of information... cation of structural knowledge to establish the But let us be optimists. Some issues are genes’ functions, based on statistical and amenable to specific treatment, providing ways bioinformatic techniques). to deal with given orders of problems. Follow- “The fundamental strategy (...) is to expand ing the line of thinking of Lesgards, Sheps, and the scope of biological investigation from study- Tarnero, an argument worthy of note is devel- ing single genes or proteins to ‘studying all genes oped by Gilbert Hottois (1994), noting that or proteins at once’ in a systematic fashion (...) “what characterizes modern science is the break [my emphasis]. Functional genomics promises with symbolic discourse and metalinguistic to rapidly narrow the gap between sequence speculative knowledge. Neither technique nor and function and to yield new insights into the mathematics belongs to the order of language behavior of biological systems” (Hieter & Bo- (...). Games are created which are not new lan- guski, 1997, op. cit: 601). guage games, although language is not totally The article quoted above describes stud- excluded and frequently intervenes (...). Within ies ranging from the completeness of yeast these games (...) things are not decided through genomes to genetic approaches to the diagno- conversation, but through calculation (increas- sis, prognosis, and treatment of cancer that ingly performed by computers) and technophys- could already be included under this new ical exchange, whether efficacious or not (...)” “heading” (Hieter & Boguski, 1997). Strictly (Hottois, 1994:63). From this perspective, to speaking, will “functional genomics” turn out study the concept of information would ap- to be (or is it already) an important field, and pear fruitful. will it thus merit our efforts to accompany its results? FG is already being viewed as the form the human genome project will assume over Seeking information the next millennium, after the descriptive/ structural phase (Morel, 1997). Would it be ap- According to Jorge (1993), one can postulate propriate now to consider it just a passing fad three fundamental concepts for so-called mol- turning technobiosciences into a spectacle? ecular biology: information, adaptation, and For better (or for worse?), how much of each self-organization (or autopoiesis). I believe it (or both) of the above will it turn out to be? would not be outrageous to include the follow-

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ing: evolution and natural selection. Yet as we mechanisms of heredity and genetics might shall see, the notion of information is particu- come from physical laws (Dupuy, 1995). Fox- larly important and will be the object of our at- Keller (1995) points out that it was Schrödinger tention. who provided the notion of chromosome as Scholars generally establish inaugural mo- script/code. ments. With the emergence of the notion of in- According to Fox-Keller (1995), the very ex- formation as a quantifiable element, references pression “information”, with strong metaphori- tend to converge on the classical work of Shan- cal connotations since it was explored in the non and Weaver, The Mathematical Theory of 1950s by the discoverers of the DNA double he- Communication (1949), in which the authors lix, Watson and Crick, converged towards the develop a theory on the measurement of the notion of instruction. Biologist and science amount of information in a message transmit- historian Fox-Keller analyzed the evolution of ted by a communications pathway. They create the concept in the 20th century and how the the notion and the forms of mathematical original sense of the information theory was treatment of “binary digits” (bits), units of ba- not maintained in the description of the func- sic information for the functioning of comput- tioning of nucleic acids in protein synthesis. er systems and ways of calculating and deter- Furthermore, this perspective turned the ge- mining the storage capacity of these elements netic code into a “message” (see messenger for processing and transmission. In other RNA) assuming the form of “orders”. Today, the words, if computing operates on symbols, bits predominant points of view see genes as cause, constitute the units of these symbols (devoid machines as organisms, and organisms as mes- of meaning) allowing for such operations. This sages. It is essential to be clear that all language is all quite trivial for any novice in today’s com- is not only descriptive but also “performatic”, puter arts. But such were the beginnings of cy- i.e., socially constructed and context-depen- bernetics (now referred to as first-order cyber- dent, and must thus be evaluated as to its ef- netics), a discipline whose seminal text by Nor- fectiveness and not according to true/false cri- bert Wiener, Cybernetics, was published in 1948 teria (Fox-Keller, 1995). and which would deal with “information” and According to Jorge (1993), one can thus shape it into “programs”... Nevertheless, how classify molecular biologies in two fundamen- does the calculable concept of “information” tal watersheds (with intermediate areas): 1) the with high mathematical, statistical, and cyber- “official” one, based on the notion of “order netic contents extend to molecular biology? based on order”, where the living being results Maria M. A. Jorge (1993) and J-P. Dupuy (1995) from stable processes of ordered construction, trace this transition in similar fashion. Accord- by regular, unvarying repetition, such that ing to Jorge, the “intellectual infrastructure of sooner or later such mechanisms will be dis- molecular biology” is situated in the postula- covered (the human genome project appears to tion of a complementariness between physics feed on this perspective); 2) the “other” one, and genetics as postulated by Niels Bohr and the central idea of which is “order based on dis- developed by one of his disciples, Max Del- order” (or noise), where unpredictability, ran- brück. domness, instability, bifurcations, and impon- During the 1940s, studies by Delbrück’s derableness are crucial to the genesis of living group convinced him that genes were mole- beings. cules viewed from the perspective of quantum I believe, perhaps in simplistic terms, that physics. But there appeared to be a biological there are situations where both approaches principle of uncertainty which hampered an may apply (in an example mentioned above, understanding of the genetic minutiae. The the first is particularly applicable to viral, bac- two disciplines were drawn together by the dis- terial, and correlate forms and the second is covery of new laws of physics (Jorge, 1993). more in keeping with the human experience). The ideas raised by information communi- In other words, here we are with the recurrent cations theory and feedback regulation served problem of measuring the proportions of the initially as a new “language game” to approach “nature(inborn)/nurture(acquired)” conun- the phenomena of heredity and genetics. Thus drum in the constitution of various living be- emerged such concepts and terms as “informa- ings (without delving into another recurrent tion”, “program”, “code”, “message”, “transla- and thorny terrain, that of defining which liv- tion”, and “transcription”. ing beings possess a mind, whatever that is...). Another physicist, Erwin Schrödinger, asked It is also important to highlight Jorge (1993) the question in 1944 (in the form of a book), in emphasizing that the current vigor of the no- What is Life? and suggested that an answer to tion of “information” can be ascribed to the

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fact that it serves both the molecular water- temology (both in the sense of the questions as shed of order (neo-mechanism) and that of dis- to knowing and the possible answers concern- order (neo-vitalism). In the first case, the no- ing the issue of knowledge). Cybernetics looked tion is linked to calculating and processing so- at itself and proposed as its enunciates the called informational units (like bits), as applied questions as to what it means to exist, to know to the above-mentioned field of bioinformat- [and its derivations vis-à-vis observer-subject ics. If life is information – and this is the hy- (who knows?) and observed-object (what is pothesis of “ordered” molecular biology – then known?)] (von Foerster, 1991). However, one of living beings can be explained on the basis of the risks of this perspective is that of falling in- their algorithmic information content (AIC) to a kind of neo-vitalism – reduction of the bio- (Gell-Mann, 1996) [with algorithm based on logical sphere to the psychic/mental, which af- the concept of the computational machine ter all possesses particular cognitive proper- proposed by Alan Turing, “given sequences of ties. Such properties originate from emerg- logical/mathematical instructions oriented in ing “complexological” models, the “interest in a specified direction” (Atlan, 1991: 217), or which”, according to Atlan (1991), “lies in estab- more simply, as a rule (or set of rules, i.e., pro- lishing how structures and functions are program) to calculate/compute something (Gell- duced that play the role of creating meanings in Mann, 1996)]. the eyes of an objective observer. From there on, From this perspective, the complexity of bi- such models are confused with the immediate, ological systems can thus be measurable and unique experience of our subjectivity (...) [We computable, especially allowing for manipula- confuse] the form of creativity we perceive and tions. This is the position taken by neo-Dar- describe in certain natural phenomena with winist Daniel Dennett (1995), who considers that of our own spirit” (Atlan, 1991:110). In gen- evolution by natural selection an algorithmic eral, when we approach evolutionary phenom- process occurring in the molecular record of ena in macromolecules and thereby apply in- nucleic acids. In his opinion, “Darwin’s danger- formational notions, we are proceeding to ous idea” pertains to the fact that the “algorith- analogical/metaphorical transpositions (“no- mic level is the level that best accounts for the madism”) of concepts from different orders of speed of the antelope, the wing of the eagle, the organization. This occurs whether we affirm ei- shape of the orchid, the diversity of the species ther of the following: (...)” (Dennett, 1995:59), even without the oblig- a) that evolution occurs by natural selec- ation of producing such characteristics (and by tion at the (molecular) level of algorithmic in- extension, without the need to reach us). Neu- formation contents. ronal functioning and the so-called cybernetic The above belief fosters the so-called gene systems (analogically called neural networks) fetishists, those who believe in genomics as the also obey algorithmic and thus intelligible code-of-codes, the book-of-books, the Holy rules (i.e., ones that can be modeled) from the Grail, and the gene as an exclusively material point of view of a computational neo-mecha- entity, bearer of a heavily deterministic causal nism. However, this “computational surveil- action, a thing in itself. Fetishes, as the substi- lance” of humans based on the notion of “cold, tutes they are, provide a concreteness with op- calculating information” was challenged by the erational ends for the genome. They have the so-called second-generation cybernetics move- function of making things appear well demar- ment captained by Heinz von Foerster (1991). cated and controllable, something which is oc- This Vienna-born physicist was one of the fore- casionally possible to conceive of and above all runners of the notion of information as the un- allows ones to operate. But under many cir- derlying element in self-organization by living cumstances this proposition is untenable, since beings, who work with information using re- “the reality and materiality of the genome is si- cursive, autonomous, and self-referred process- multaneously semiotic, institutional, machinic, es such that their organization of themselves organic, and biochemical” (Haraway, 1997: 99) and “reality” occurs in infinite circles, in an as- and thus depends on the context and is diffi- sociation of information with life and knowl- cult to control or predict, or edge. This occurs in humans through the speci- b) that biological systems result from the ficity of the human mind, allowing one to be ways by which organisms exchange “informa- conscious of science itself – to operate one- tion” with their milieu and we, subjects/ob- self with science (the etymological root of con- servers, study them as objects/observed in the science). form of couplings, under the premise that to Such propositions result in an approach be- exchange and process information is to know, tween cybernetics, biology, ontology, and epis- which in turn is to live...

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In humans, to live is more than to know, atic, to say the least, it is essential to distin- which is more than to process information. Yet guish between “information” as constituent currently, “‘Life’, materialized as information potential and knowledge. Knowledge is what and signified by the gene, displaces ‘Nature’, pre- actually occurs in the ordering and integration eminently embodied in and signified by old- of various “(in)formative” elements. The ratio- fashioned organisms” (Haraway, 1997:134). By nalizing discursive pressures of epidemiology the way, Dennett’s peculiar verve (1996) serves (both current and future) are undeniable, to inadvertently illustrate this shift quite clear- through its scientific models of intelligibility. ly. The American philosopher goes to the point But rather than taking them as unconditional, of calling the evolutionary process by natural ineluctable truths, it is essential to distinguish selection “Mother Nature”. Yet it would appear (within such proposals for knowledge) the that this denatured mother refuse to nurse both premises and vicissitudes of the constitution of the mineral kingdom (with its quakes and vol- their elements for our knowledge and interven- canoes) and meteorological phenomena... tion in health, in addition to their functions in Finally, running the risk of sustaining con- the possible idiosyncratic interpretation and ceptual stances whose ideological spin-offs creation of meanings in the lives (however they and sociocultural repercussions are problem- may be...) of each and every one of us.

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