what toll pursuit

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What Toll Pursuit: Affective Assemblages in Genomics and Postgenomics

Mike FortunDepartment of Science and Technolog Studies

!ensselaer Poltechnic "nstitute##$ %th Street Tro& '( #)#%$fortum*rpi+edu

Toll! Gate

"n the late #,-$s .hristiane '/sslein01olhard and 2ric Wieschaus& 3orking at the Ma4

Planck "nstitute in T/bingen on the genetics of Drosophila development& developed their

e4perimental sstem for producing tens of thousands of mutant fruit fl embros 5see 6eller

#,,7& #,,-8+ As an 9e4perimental sstem& their saturation screen using chemical mutagens

produce not onl novel 9epistemic things but& e;uall important for this essa& surprised

scientists 5!heinberger #,,%8+

a toll? 5@ansson

and 2dfeldt )$$8 or perhaps simpl 9Toll? 5Weissmann )$#$8+ Although accounts differ& there

is agreement on the need to provide an e4clamation mark+ This has been most fre;uentl

translated from the German to the 2nglish signaling path3as as 95That 3as8 Weird?& but 95That

3as8 .ool? also has currenc+ The possibilities merit further complication later+

Beaving the con>oined instabilities of histor and translation aside for the moment& " note

here onl that their e4perimental sstem& innovative as it 3as& 3ould be almost certainl be

described b professional historians of science as 9genetic and not 9genomic& let alone as

9postgenomic+ 'o one at the time 3as talking about human genome pro>ects& or genome

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pro>ects for an other organism& for that matter+ Although their overall pro>ect had a vaguel

0omic intentCto catalogue& completel& all the developmentall important genes of Drosophila C

h>istorians 3ould still sa that their sstem 3orked in a genetic fashion& b creating and

maintaining the lines that allo3ed for isolating the effects of particular mutant genes&

characteri=ing them functionall or structurall at the molecular level& but 3ith little or no use for

or interest in D'A se;uence+

"ndeed& it 3asnt until #,%% that 6athrn Anderson 5a close colleague of '/sslein0

1olhards8 cloned toll and sho3ed it to code for a transmembrane protein+ "t 3ould be another

five ears before the ne4t set of trul surprising results 3ere produced+ Eet3een #,, and #,,7&

Eruno Bemaitre and ules @offman 5among others8 had established the ke role of toll in a

different signaling path3a& one that provides the fruit fl 3ith protection against infection b

Aspergillus and other fungi& as 3ell as Gram0positive bacteria: a 9developmental gene had

une4pectedl become an 9innate immunit gene 5Bemaitre )$$H8#+ Eut although the @uman

Genome Pro>ect had b then been debated and begun 5debates 3hich resulted in the inclusion of

Drosophila and other 9model organisms in the pro>ect8& and 3hile D'A and protein se;uence

information had provide a number of interesting e4perimental clues and theoretical insights in the

research linking development to immunit& much of this 3ork could still be called 9classical

genetics and biochemistr+ "n a #,,7 article revie3ing this research and discussing the

evolutionar significance of the toll and other signaling path3as I path3as apparentl

developed before the plant0animal divergence as common protective mechanisms& and onl later

conscripted into developmental intricacies I Marcia Eelvin and 6athrn Anderson never once use

the 3ords 9genome or 9genomic 5Eelvin and Anderson #,,78+

1 Bemaitre notes the element of serendipit involved in these e4periments: 9" no3 reali=ethat our success in identifing the function of Toll in the Drosophila immune response3as partl because 3e routinel used a mi4ture of Gram0negative and Gram0positive bacteria to infect flies& 3hereas other groups onl used Gram0negative bacteria+ TheGram0positive bacteria strongl activated the Toll path3a and enabled us to discern therole of TollJ 5Bemaitre )$$H: )H0)8

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"t 3as around that time that researchers in .harles ane3as reno3ned immunolog

group at (ale cloned the first human gene coding for 3hat 3ould become kno3n as a 9toll0like

receptor 5Med=hitov& Preston0@urlburt& and ane3a #,,-8+ A ke part of that 3ork stemmed

from searching the human gene se;uence database at the 'ational .enter for Eiotechnolog

"nformation I this 3as three ears before even a 9first draft of a full human genome se;uence

3ould become available& i+e+ before 9the @uman Genome Pro>ect is conventionall said to have

been completed 5in )$$$8& i+e+ some3here in the midst of the 9genomic era+

ane3as group had been e4pecting at the time to find a .0tpe lectin domain encoded

in the clone the 3ere bro3sing for+ !uslan Med=hitov later recalled the groups 9initial

disappointment that their database search did not produce that result& but instead turned up a

homolog to a Drosophila gene 5Med=hitov )$$,8+ "t 3as onl then that the learned about the

9stunning discover 5ibid+8 of Bemaitre and @offmanK it seems that sometime in #,,7 @offman

sho3ed ane3a a photograph 5later the cover image of the September #,,7 Cell issue 3hich

bore their paper8 of 9a Toll0receptor deficient fl overgro3n 3ith aspergillus hphae at a grant

meeting of the @uman Frontiers in Science in 3hich the collaborated+ ane3a had his o3n

9Toll?0like moment+

ane3as lab thereb initiated a ne3 phase in the understanding of the mechanisms of

innate 5rather than adaptive8 immune response in humans& and populari=ed the ne3 acronm for

toll0like receptor& TB!& that 9as an abbreviation 3as soon 9fast becoming as famous as !'A or

D'A& evidenced b over #-&$$$ papers listed in PubMed in the follo3ing decade 5Weissmann

)$#$8+ TB!s are 3hat ane3a called 9pattern recognition molecules that are important nodes

in the comple4 signaling path3as of cellular response& biosemiotic path3as that include

numerous other proteins as 3ell as the more 3idel famed !'A and D'A+ Such signaling

path3as are hallmarks of 9postgenomics& 3here agenc and action are distributed rather than

centrali=ed in the gene& 3here codes become variabl interpreted signals& and an apparentl

immaterial 9information is al3as instantiated in material processes of 9transduction+

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Eut " recount these brief stories not to demarcate geneticLgenomicLpostgenomie eras& but

to sidestep the historical demarcation problematic altogether+ M intent is to pluck out from the

immense flo3 of events in this era& 3hatever 3e call it& a fe3 episodes that highlight hho3

scientific change is affective as much as it is cognitive& instrumental& e4perimental& and

institutional+ While those latter differences are indeed interesting and important to comprehend&

the differences " am more interested in here ma be summed up as: differences in 9Toll?0like

e4pression level+ A significant change in the broader genetic0genomic0postgenomic histor& of

3hich the opening narrative above is a condensed and simplified metonm& is the increasing

capacit of the different e4perimental sstems to generate t3o different but ent3ined affects&

surprise and interest I surprising& interesting& unprecedented ob>ects like toll0like receptors& and

surprised& interesting scientific sub>ects 3ho e4claim something like 9Toll? These affective

assemblages 3ill be difficult to assa& as 3e have limited methods and idioms for articulating

these kinds of affective events+ We need& then& ne3 idioms in the varied public spheres in 3hich

contemporar science is debated& evaluated& funded& and valued as a social resource& to better

understand the kind of science that genomics has become in postgenomics+

Stated some3hat differentl: among the man signs 3e might use to distinguish genetics from

genomics from postgenomics I immense and ever0accumulating databases& ever0accelerating and

increasingl economic se;uencing rates& more and larger databases 3ith higher degrees of

specificit and interconnection& robots cheap and e4pensive& a plethora of >ob ads for

bioinformaticians I there is a relativel neglected one: a comple4 affective response from

scientists for 3hich 9Toll? serves as a useful marker+ What might 3e fish out of the historical

archive of genomics and postgenomics using this marker& and might we in turn be surprised And

conversel& 3hat might 3e seek to add to future historical archives of 3hat03ill0have0been0

postgenomics that 3ould further enrich those other signaling path3as& in 3hich the capacity for

being surprised and interested is a goal pri=ed in the sub>ects of science& as 3ell as the political

and social 3orlds in 3hich those sub>ects live and 3ork

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2ven a preliminar test of these hpotheses 3ill be a long time coming& but might

incorporate current behavioralLenvironmental postgenomic e4plorations of ho3 the startle

response of =ebrafish ma be stunted b e4posure to lead 5see !ice et al+ )$##8 or other

environmental to4ins+ We could use the interesting results generated 3ith that model organism

3ork to scan human databases for promising homologous genes involved& before moving on to

e4tensive GWAS studies comparing the distributions of alleles associated 3ith startle0behavior

among postgenomicists to that of a control population of& sa& historians+ "n earl preparation for

that 3ork& here " begin onl to briefl theori=e this scientific sub>ect as assembled from the

fundamental affects that pschologist Slvan Tomkins named 9surprise0startle and 9interest0

e4citement 5see Tomkins )$$%K Sedg3ick and Frank #,,K Wilson DAT28+

Tomkins described eight 5sometimes nine8 basic affects: interest0e4citement and

en>oment0>o 5the positive affects8& surprise0startle 5the onl neutral affect8& and the negative

affects distress0anguish& anger0rage& fear0terror& shame0humiliation& and dissmell0disgust+ The

doubled terms are meant to conve the range of intensit in 3hich the affect ma be e4perienced+

Affects are distinct from the more comple4 emotions that are co0assembled from the affects along

3ith scripted cognitions+ 2motions& in short& are 3hat contemporar anthropologists 3ould call

9biocultural& 3hile for Tomkins affects are a decidedl more phsiological event& in the sense of

being the propert of a developing human organism as it encounters and responds& from birth& to a

changing 3orld+

9Surprise0startle is the affect " believe is embodied in the Toll!-like response that " have

signaled 3ith hereK it 9is ancillar to ever other affect since it orients the individual to turn his

attention a3a from one thing to another 5Tomkins )$$%:)-8+ Surprise is 9a general interrupter

to ongoing activit I such as straining our ees over the )-th fruit fl embro of the da under

our microscope& or algorithmicall aligning the se;uence of one more chromosome

microfragment 3ith that of another in the publicl0funded and 0accessible database ouve been

laboring on for the previous eight ears+

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Bater& " e4plore in detail some of 9surprises of the @uman Genome Pro>ect& as

recollected and e4pressed b a number of its leading figures& but " 3ould argue more generall

that the Toll!0like response of surprise is the affect produced b an effective e4perimental sstem

3hen it produces 3hat !heinberger terms the 9unprecedented+ Surprise0startle is a 9circuit0

breaker 5ibid+8& a shatterer of habits& that prompts a 9re0orientation+ "t is the response to 3hat

2veln Fo4 6eller 5#,,:))8 calls 9the funn thing that happened on the 3a to the @ol

GrailCthe interruption of the e4pectation that 9it might be a big code but its still >ust code& the

reali=ation that the code 3as al3as alread broken or at least noisier and more open to multiple

determinations than one dreamed& that ever center and ever command and ever imagined

master 3as decentered and disrupted and sub>ect to deferred interpretive orders

With the increasing amounts of bio-information of all kinds produced daily by the

investments in and of the Human Genome Project, is it any wonder that funny things would

happen – that interruptions and surprises would mount? Why were we surprised? Maybe we

wouldn’t have been so startled if we had learned to pay attention to the affective register of

scientific developments.

9"nterest0e4citement is the other related affect animating the postgenomic sub>ect+ !e0

oriented b the surprise0startle affect& a postgenomicist becomes interested in the accumulating

information& 3hich reinforces the interaction& driving the entire e4perimental sstem for3ard into

ne3 unprecedented futures+ Bike surprise& interest is elicited b something that couldnt be

simpler I difference& as registered b 9neural firing:

"t is our belief that it is possible to account for e4citement on a single principleCthat of a

range of optimal rates of increase of stimulation densit+ E densit 3e mean the product

of the intensit of neural firing times the number of firings per unit time+ 5ibid+:#%-8

We postgenomicists are interested b difference+ The greater the difference I in intensit&

or in number I the more neural activit& the more interest0e4citement+ And the more interest0

e4citement& the more one cares:

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The interrelationships bet3een the affect of interest and the functions of thought and

memor are so e4tensive that absence of the affective support of interest 3ould

>eopardi=e intellectual development no less than destruction of brain tissue+ To think& as

to engage in an other human activit& one must care& one must be e4cited& must be

continuall re3arded+ There is no human competence 3hich can be achieved in the

absence of a sustaining interest& and the development of cognitive competence is peculiarl vulnerable to anomie+ 5ibid+:#%%8

24citement can be 9massive& but need not beK it is 9capable of sufficientl graded&

fle4ible innervation and combination to provide a motive matched to the most subtle cognitive

capacities 5ibid+#%,8+

"n the remainder of this essa& " anal=e some episodes in the development of some of the

9subtle cognitive capacities of postgenomics I indeed& it ma be a fairl good heuristic to think

of postgenomics as 3hat results 3hen the comparativel coarse& crude& boorish and 9boring

genomics becomes someho3 more subtle+


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institutions& and 5e408.2oed more freedom

and privilege to find more e4citement in genomic speculation than the assistant professor& post0

doc& or technician 3orring about the tedious and repetitive demands of grant3riting& marker

characteri=ation and development& and ;uotas of D'A se;uence to be fulfilled+ (our toll 0age

ma var+

Some such social analsis is certainl possible and necessar& as 3ill be seen belo3+ Eut

3e shouldnt e4plain a3a too ;uickl the force and logics of comple4 affective states& and their

possible importance for understanding scientific change over time+

@aving used affect and collective mood to set the historical stage and open his essa& Gilbert

never again invoked it+ Affect faded into the background and became invisible& giving 3a to an

e;uall comple4 amalgam of arguments about the reigning biological paradigm and the one

Gilbert glimpses emerging from it+ This comple4 amalgam of arguments 3as framed b a

statement that is neither inside nor outside Gilberts te4t& an e4clamation that appeared onl in the

subtitle& and emanated from an editorial rather than authorial position: 9The stead conversion of

ne3 techni;ues into purchasable kits and the accumulation of nucleotide se;uence data in the

electronic data banks leads one practitioner to cr& OMolecular biolog is dead I Bong live

molecular biolog? 5ibid+8 Gilberts 9o3n trope for paradigm change 5that is& the one that

clearl occurs inside his authored te4t8 3as more definitive in its invocation of a 9break& and

more .hinese than French in historical connotation: 9Jthe vie3 that the genome pro>ect is

breaking the rice bo3l of the individual biologist& he suggested& 3as a vie3 that people had to

get over+ 5ibid+8

Despite his attunement to the revolutionar potential of genomic kits and data& Gilbert did

not envision increased surprise& e4citement& or similar toll 0like affect as one of the outcomes

characteri=ing the ne3 era+ 9The tenfold increase in the amount of information in the databases

3ill divide the 3orld into haves and have0nots& Gilbert predicted& 9unless each of us connects to

that information and learns ho3 to sift through it for the parts we need 5ibid+K emphasis added8+

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Genomics or postgenomics is& in this vie3& predicated on fulfilling 3hat 3e alread kno3 3e

need and 3ant& >ust faster and more efficientl+ There is not reall a sense that the needs

themselves could& should& or 3ould be transformed+

9Se;uencing is boring 3as indeed a fre;uent declaration in the debates in the mid0 and

late0#,%$s leading to the institutionali=ation of the @uman Genome Pro>ect+ ames Watsons

personal aversion to anthing boring& especiall boring people& has been 3ell broadcasted

5Watson )$$-8+ Still& his concerns about boringness are 3orth taking into account& reflective as

the are of broader cultural patterns+ 2arl in his brief directorship of the @GP& Watson spoke in

#,,$ 5around the time of Gilberts article8 about the problem of non0e4citement at the American

Academ of Arts and Sciences in .ambridge& MA:

TQhe people 3ho 3anted to do it the @GPQ 3ere all old and almost retired& and

everone oung 3as against it& because the figured if 3e did it& it 3ould take mone

a3a from their research+ So all the people ou normall 3ould e4pect& because theRre

going to do something& 3ere against it& and all the people& ou kno3& 3ho reall almost

stopped doingQ science& 3ere in favor of it+ 'o3 that includes me: " 3as reall in favor

of it& as 3as Paul Eerg+ And ou could sa that the ob>ective 3as a 3onderful ob>ective+

WhatRs more important than this piece of instructions Eut everone else felt essentiall

frightened+ "t 3as going to be big science& it 3as going to be ver boring 00 >ust

determine all these letters 00 so anone 3ho 3ould do it is someone ou 3ouldnRt reall

3ant to invite to dinner an3as+

And it 3asnt simpl se;uencing that 3as regarded as boring& in Watsons vie3K the development

of high0resolution genetic maps provoked a similar affective response:

J The trouble about getting these genetic maps& 3as that doing it 3as ver boring& and in

fact David Eotstein had put in a grant application and had been turned do3n b '"@: it

3as too dull to be good science+ Eut in fact it 3as a sort of tool that ou reall needed+

'ot onl are affects al3as amalgamsChere& it should be evident that Eotstein& at least&

found some e4citement in the boring 3ork of developing better genetic mapsCbut these affect0

amalgams are al3as assembled to epistemic ob>ects and their larger cultural 3ebs+ This is part

of the reason 3h affects tend to disappear from vie3: debates about tools and big science& for

e4ample& are 3ell0recogni=ed concerns of historians& sociologists& and philosophers of science

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and technolog I and of scientists and engineers& too+ So 3hat does it reall matter if Watson&

Eotstein& or an other scientist is bored& 3hen more social and collective things are at stake

" promise to return to such ;uestions& 3hich are anthing but boring 5to me& an3a8+

For no3 lets follo3 Watsons remarks& 3hich prompted an interesting e4change 3ith Matthe3

Meselson

Matthe3 Meselson: im& in Drosophila& " donRt kno3 of a single gene that has been gone

after intelligentl& that hasnRt been cloned 3ith a little effort& even though 3e donRt have

the complete se;uence of Drosophila+ So " gather that 3ith humans& itRs different& because

3e canRt do genetic crosses and certain other manipulations as 3ell 3ith humans 00 but

the might come along+ So " 3ould like to hear ou e4plain 3h this pro>ect is soQ

necessar for humans+++

Watson initial response I 9" think its necessar in Drosophila& >ust because to get them all to cost

00 if 3e can do it at one0tenth the cost that itRs being done in our lab& eventuall it 3ill be cost0

effective+ "t 3onRt be cost0effective if ou do it at five to ten dollars a base pair& but if ou do it at

fift cents a base pair& ouRll get it outJC3as hardl satisfactor to Meselson: 9Thats a

different reason& Meselson argued back& one having little to do 3ith doing science

9intelligentlCi+e+& not b boring rote brainless mechanical meansCso he re0stated his

ob>ection:

Meselson: 'ot a single important gene that anone has gone after intelligentl has failed

to be cloned and se;uenced+

Watson: (eah& but there is a lot until 3e do it that ou donRt kno3 the e4istence of& and

the ;uestion is if ou actuall see the total thing& 3ill ou be surprised and get interesting

scientific insights And m guess is ou 3ill& but thatRs m+++

Meselson: ThatRs a different reason than the one ou gave+ ThatRs a good reason+

Nnlike Gilbert& for Meselson productivit and efficienc are not particularl good reasons

for dedicating billion in public monies to something like the @GP I but to 9be surprised b

9the 3hole thing and get ne3 9interesting scientific insights That"s a good reason+

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'o3 9good reason ma mean onl a reason shared 3idel 5enough8 in the scientific

culture of 3hich Meselson and Watson are 5elite8 members I 9Nne4pected surprises Sounds

good to me? Eut 3hat if it really is a good reason 00 meaning& 3hat if there 3ere a shared

understanding of a good societ as one 3hich contained& and cultivated& scientists 3anting to be

surprised

"ts also 3orth remembering that even non05elites8 en>o their affects& so " use m toll-

like probe to pull up one more remembered event concerning these pre0postgenomic ears+

Going into m basement and accessing m dead0tree database& " found an intervie3 " did as a pre0

posthistorian of science graduate student 3ith !obert Mo=is& then a leading scientist in the N+S+

Department of 2nergs genomics programs+ We had been talkingCthis 3as also in #,,#Cabout

the histor of earl meetings sponsored b D


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challenge+ And man of the people at that Santa Fe meeting& " think& had that kind of

mentalit+

+++" think itRs reall after the #,%7 .old Spring @arbor meetingQ that a lot of the

apologi=ing and sort of re03riting of histor to sa& 3hatRs the scientific >ustification that

the Department of 2nerg is involved in this& reall began+ So ouRve got a stretch there

of perhaps almost months 3here& from m vie3point& that issue 3asnRt even discussed+ "t3as still& 3e can do this& itRs 3orth doing& and it might actuall be some fun doing& for a

lot of cra= reasons+ And " think it 3as certainl al3as discussed that there 3ould be all

these biomedical paoffs& but a lot of the initial plaers " donRt think 3ere even looking at

it from that perspective+

For Mo=is& the 9intellectual >ustifications for doing a @uman Genome Pro>ect& 3hile clearl

9not incorrect& 3ere nevertheless secondar to 9fun and related 9cra=

coolLa3esomeLe4citingLtoll!Q reasons+ Promises of 9biomedical paoffs and other such rational

>ustifications 3ere certainl crucial to packaging& branding& and selling the @GP to its funders in

the N+S+ .ongress& but it 3as the 9intellectual challenge of assembling a massive 9pu==le that

causes it to be 9dreamt up+ 5"ts 3orth recalling that in the 6uhnian paradigm of scientific

change& 9pu==le0solving is the mundane& perhaps boring 3ork of 9normal non0revolutionar

scientists& not a challenge for fruitcake revolutionar ones+8

"ve used these fe3 episodes and recollections to characteri=e one aspect of resistance to

a centrall0organi=ed effort to develop the sciences and technologies of genomics in the #,%$s as

predicated on its being 9boring I i+e+ not eliciting the affect of interest0e4citement+ Such

resistance to the @uman Genome Pro>ect 3as fairl 3idespread& 3ith a far more comple4 ;ualit

that simpl 9its boring& and 3ith its o3n histor& in 3hich soe resisters 3ho 3ere critical of

soe aspects of soe of the pro>ect definitions that 3ere put for3ard in the mid0to late0#,%$s&

came to be supporters of the @GP as its institutional and scientific definition emerged from

various e4pert committees and bodies 5see Fortun )$$)8+ These affect threads 3ere 3oven

together 3ith institutional turf politics and their attendant mi4 of scientific and ideological

3 Authors intervie3 3ith !obert Mo=is&


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arguments about the shape and form of the @GP+ "n those e4pert discussions& 3hich resulted in a

less se;uence0obsessed and more mapping0inclusive pro>ect as 3ell as the inclusion of various

9model organism genomes along 3ith the human& the Department of 2nerg and its scientists

3ere often troped as rather mindless& good onl for tool0building or engineering0tpe

technological problems 5sorting cells& building and shipping chromosome libraries& banking but

not anal=ing data& etc+8 3hile the forces of the 'ational "nstitutes of @ealth 3ere ones of

creativit& able to pose and ans3er actual biological research ;uestions+ Eecause the Dect8 confessed that he 3as

thoroughl ama=ed+++at ho3 the biomedical communit could oppose this pro>ect:

" cannot believe that ou are going to insist on business as usual in this field+ "t is

beond m comprehension& " repeat& beond m comprehension+++

(Qou cannot sit here and tell me that in all of the research that is going on 3ith

the marvelous individual investigators+++ou cannot tell me there is not more than )$$

million& that if 3e even asked ou to go look& ou 3ould sa probabl 3ent for

naught+++People had a lot of fun+ Scientists had a lot of e4citing mental activities+ Eut it

is inconceivable that out of - billion in grants in this ver heralded !


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The statement can be read as indirect confirmation that 9fun& or the more clumsil

phrased 9e4citing mental activities& is an important driver of scientific activit+ 2ven senatorsC

3hose understanding of science 5among other things8 is notabl limitedCunderstand this+ Eut

Domenici also understood that platime& in 3hich 9marvelous individual investigators got paid

3ith public dollars to tr to surprise themselvesCeven if platime 3as also its opposite&

9business as usualCthat platime 3as no3 over& and it 3as time to get on 3ith the more serious&

un0fun& and boring 3ork of tool0making& manufacturing the 9hard3are and ne3 technolog and

ne3 techni;ues of the @uman Genome Pro>ect+

Genomic Mandala

"f the idea of loads of D'A se;uence information in the mid0#,%$s elicited a Toll ?0like

affect in 3hich 9boring predominated over 9interesting& it didnt seem to take long for that

affect0almagam to invert its composition+ E the mid0#,,$s& onl a fe3 ears into the distributed&

dedicated& federal ta4 revenue supported& multi0organismal se;uencing and mapping efforts

shorthanded as the @uman Genome Pro>ect& being hit 3ith a flood of se;uence informationCand

it indeed seems to have been dramaticall phsicalC3ould elicit surprise and e4citement& 3ith

barel a tinge of boredom+

An informative marker for this shift is the #,, publication of the full se;uence and map

of #aeophilus influen$a& signifing for some 9the real launch of the genomic era 5'elson and

White )$#$:#-)8+ Popular science 3riter .arl Vimmer notes that the publication of the #+%

million base pair se;uence landed 93ith a giant thwop& disrupting 3hat he 3rl called 9the

dark ages of the t3entieth centur, 3hen a scientist might spend a decade tring to decipher the

se;uence of a single gene 5Vimmer )$#$8+ 2ven though there 3erent 9a lot of big surprises

about the microbe itself& Vimmer recalled that 93hat 3as remarkable 3as the simple fact that

scientists could no3 se;uence so much D'A in so little time+ Moreover& that remarkable fact

3as transmitted in an instant& through the 9kaleidoscopic 3heel mapping all #-H$ genes: 9"t had

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a hpnoti=ing effect& like a genomic mandala& reflected Vimmer& and 9looking at it& ou kne3

biolog 3ould never be the same 5ibid+8

9And etCsameness al3as returns to level surprising differenceK boredom re0asserts its

persistence in the interest affect0amalgam+ 2ven as genomicists 93itnessed aspects of microbial

diversit beond 3hat had been previousl appreciated in the ears follo3ing the kaleidoscopic

hit of the #% influen$a genome& the mounting number of these 9surprises generated b the ne3

se;ucncing capacities did not take long to simpl become 93idel accepted features of the

increasingl post0 genomic landscape and life3orld+ Vimmer dubbed it the 9(et0Another0

Genome Sndrome 5Vimmer )$#$8

Surprises of the @GP

And so& pointing out genomic surprises became something of a dull routine b the time

the @GP had been rituall marked as completed in )$$$+ 9"t appears no3 that hardl a 3eek

passes 3ithout some ne3 insight into the 9genome taking us b surprise& noted biologist

!ichard Sternberg 5Sternberg )$$):#8+ Eut despite their fre;uenc& and the gro3ing fre;uenc

3ith 3hich the 3ere thus noted& surprises still remained largel anomalous or background

9color to the main stor+

@ere " note a fe3 of the other ob>ects or events that elicited surprise and interest among

genomicistsK se;uence information itself 3as an important but not the onl part of these surprises+

To its credit& 3hen .old Spring @arbor introduced an oral histor collection on 9Genome

!esearch to its 3ebpages& in addition to topical sections like 9Mechanics of the @GP&

O.hallenges of the @GP& and 9Gene Patenting& it also sa3 fit to ask its intervie3ees 5all male on

this topic8 9What surprised ou the most The affective register on displa here is right on the

surface I postgenomics turned out to be surprising& interesting& e4citing& Toll!, anthing but

boring+

17


18/28

Perhaps the biggest and most publici=ed surprise 3as the number of human genes in the

genome coming in much& much lo3er than e4pected+ Se;uencing0innovator Eruce !oe& 3ho led

the group at the Nniversit of ust looking at 3hat the designer did+H

!obert Waterston mentioned another no3 3ell0kno3n surprise of postLgenomics& 9that

fift percent of the 3orm genes are shared 3ith people& and fift percent of human genes are

shared 3ith 3orm or something like that+ "ts >ust astounding+ The re0orienting of evolutionar

histor and theor is a big part of m opening stor of toll0like receptors& as researchers follo3ed

genes& gene functions& and gene se;uences from fl to human and beond& re0orienting much of

immunolog in the process+

"n this series of fireside chats 5metaphoricall and literall I these intervie3s 3ere mostl

shot over a fe3 das in front of a .old Spring @arbor fireplace8& 2ric Bander departed the most

from se;uence0centrism and 3a4ed Weberian:

What surprised me most"n the end& ho3 satisfing it 3as personall+ That0" 3ent into the pro>ect as a relativeloung scientist+ " began to get into the human genome pro>ect at the age of thirt+ At that point& ou do things cause ouRre oung and hotheaded and competitive and all sorts ofthings+ @aving no3 devoted fifteen ears of m life to this& itRs a ver large piece of it andat some point " came to have0mabe about half 3a through0>ust a tremendous affectionfor the people& m colleagues doing it+ A tremendous feeling like this 3as a purposemuch greater than an of us& much bigger than me+ "t 3as the first time " felt like " 3as a part of something much more important than " 3as and 3ith a much greater purpose and

something that 3ould live far beond me+ That 3as 3h 3hen the .elera thing camealong and .raig 1enterQ came along aiming to kill this& " probabl reacted more stronglthan anbod in the pro>ect& more violentl in m reaction than anbod in the pro>ect because this mattered+ "t mattered to get right+ "t mattered because for me this 3as& ou

4 http:LLlibrar+cshl+eduLoralhistorLintervie3Lgenome0researchLsurprises0hgpLroe0

surprises0hgpLK recorded ), Ma )$$+5 http:LLlibrar+cshl+eduLoralhistorLintervie3Lgenome0researchLsurprises0hgpLsurprises0hgpLK recorded # une )$$+

18

http://library.cshl.edu/oralhistory/interview/genome-research/surprises-hgp/roe-surprises-hgp/http://library.cshl.edu/oralhistory/interview/genome-research/surprises-hgp/roe-surprises-hgp/http://library.cshl.edu/oralhistory/interview/genome-research/surprises-hgp/surprises-hgp/http://library.cshl.edu/oralhistory/interview/genome-research/surprises-hgp/surprises-hgp/http://library.cshl.edu/oralhistory/interview/genome-research/surprises-hgp/surprises-hgp/http://library.cshl.edu/oralhistory/interview/genome-research/surprises-hgp/surprises-hgp/http://library.cshl.edu/oralhistory/interview/genome-research/surprises-hgp/roe-surprises-hgp/http://library.cshl.edu/oralhistory/interview/genome-research/surprises-hgp/roe-surprises-hgp/


19/28

kno3& this 3as a calling in life and a purpose in life and nobod 3as going to go andscre3 it up like that and turn it into some private thing and not let us get the benefits fromitJ" canRt imagine a more 3onderful thing to have done in life+ And that surprised me+ "guess " didnRt ever imagine that it 3ould end up meaning so much+7

ust to clarif: " admire that Bander 3a4ed Weberian& and " 3ould shout Toll! if there

3ere more of a Wissenschaft-als-&eruf tone to our public discourse of science no3+ Mabe " >ust

have a soft spot for BanderK in #,,$ he 3as the first person " ever formall intervie3ed 3hen "

3as a larval historian of science& and " 3as impressed then b his generosit& honest& and his

insistence that the metaphor most appropriate to the @uman Genome Pro>ect 3as not the 9@ol

Grail but the less e4citing& more public0infrastructure0oriented 9!oute


20/28

Genomicists 3ere surprised b themselves+ "n the conclusion& " return to this labrinthine

dimension of scientific 3ork& in 3hich the ama=ement generated in the doing of science is an

affective effect of its ma=e0like ;ualities& and one is alternatel over3helmed and e4hilarated 5as

3ith an encounter 3ith a sublimit8 Eut ne4t " consider ho3 these brief& fragmentar glimpses

of the affective dimension of postgenomics become difficult to account for& hard to assimilate into

a sstem of historical or social value+

Accounting for Genomics

Beapfrog again no3 to ten ears after the ceremonial 9completion of the @uman

Genome Pro>ect+ The New 'or( Ties, 3hich had long e4uded nothing much short of unalloed

enthusiasm for the @GP and ever milestone discover 3ithin that vast enterprise& conveed a

tone of disappointment that suddenl seemed to be ever3here in a )$#$ editorial:

#$ ears later& a sobering reali=ation has set in+ Decoding the genome has led to stunning

advances in scientific kno3ledge and D'A0processing technologies but it has done

relativel little to improve medical treatments or human health+ 5'e3 (ork Times )$#$8

"f the 9advances in scientific kno3ledge and technolog here said to be 9stunning 3ere& in fact&

stunning& it 3ould be hard to imagine the sentence and the editorial moving on so ;uickl& in the

same sentence& to that dismissive 9butJ of accountabilit+ " hardl e4pect the editorial board of

the New 'or( Ties to be trul stunned b anthing& including their o3n role in building

enthusiasm for 3reckless invasions that kill millions& but " 3onder ho3 an editorial 3ritten 3ithin

a culture 3hich had a greater capacit to conve and trul share in the scientists sense of

stunningness might read differentl "nstead its >ust: stunning, yeah sure, but they haven"t

e)actly cured anything li(e they proised to when they cashed that *+ billion chec( we gave

the, have they

'icholas Wade echoed the >udgment and the rhetoric in an accompaning article:

For biologists& the genome has ielded one insightful surprise after another+ Eut the

primar goal of the billion @uman Genome Pro>ect C to ferret out the genetic roots of

20


21/28

common diseases like cancer and Al=heimers and then generate treatments C remains

largel elusive+

9Genomics is a 3a to do science& not medicine& said @arold 1armus& president of theMemorial Sloan06ettering .ancer .enter in 'e3 (ork& 3ho in ul 3ill become thedirector of the 'ational .ancer "nstitute+ 5Wade )$#$8

"t is as though surprise and insight 3ere a dime a do=en& last ears ne3s& and could not

reall disturb the calculations of 3orth that 3ere being eagerl assessed+ And it 3ould do little

good to point out the I iron chadenfreude Ithat man historians& feminist philosophers&

sociologists& and more than a fe3 postgenomicists themselves had been making almost e4actl

that prediction about the e4pected medical benefits of the @uman Genome Pro>ect for an

number of ears+ They 3ere not surprised 3hen the relationship bet3een genomes& illness& and

medicine turned out to be more complicated than hoped or predicted b the more hardcore

genome0as0Grail advocates+

What ne3 genre of science 3riting could take account of the Toll!-like emergence I both

andLor neither science andLor medicine& both andLor neither immunolog andLor genomics I of the

famil of toll0like receptors& and their fantastic evolutionar histor that binds human to halibut& a

histor that includes the evolutionar repurposing 5surel that is 9the designer 3hich Eruce !oe

invoked above8 of 9genes for innate immunit into 9genes for embronic development

Public discourse on postgenomics I and similarl multi0scale& distributed& comple4& public0

resource dependent scientific pro>ects& such as the sciences of climate change 52d3ards )$#$8C

needs ne3 genres of science 3riting that are patient 3ith the difficult demands of interpretive

multiplicit and openness& transparent to3ard and tolerant of comple4ities and ambiguities

5marked here b m doubled Toll! sign8& et resolute in their recognition and embrace of

genuinel creative& better science+

Postgenomics has indeed gotten to be 9better science 5Fu>imura and !a>agopalan )$##8

than genomics 3as: more subtle& less determinist& more attuned to the fle4ibilities and limits of its

o3n categories& techni;ues& and analtic concepts+ " read Fu>imura and !a>agopalans article0

21


22/28

ending evaluation of ho3 the developing theories and practices of genotpe variation in large0

scale populations have& over time& become 9better science on these multiple registers: 9better

scientificall& ethicall& affectivel+ 9Eetter for me also means 9more careful& 3ith that term

again amalgamating the cognitive 3ith the ethico0pragmatic 3ith the affective+

"n the larger pro>ect of 3hich this essa is a part& "m re0orienting m positive affects

to3ard a better ethnograph of these better sciences& focusing on asthma researchers

incorporating postgenomic findings and practices into a larger ecolog of diverse sciences& from

air ;ualit modeling to pschosocial stress measurement to environmental and anti0povert

activism+ "n that stor& no gene ever came an3here near to master0molecule magic0bullet hol0

grail territor& et postgenomicists have found much of interest+ Toll0like receptors are one small

part of that interest0net3ork& and like all the other multitudinous distributed parts& their signaling0

effects are al3as partial& sometimes contradictor& dispersed in une4pected 3as bet3een and

3ithin thoroughl mongrel populations& in pla onl at certain stages of development and under

the s3a of variable environmental conditions from the microbial flora of the gut to the o=one

and particulate matter levels of N+S+ cities maintained at deadlier0than0necessar+ (et " admire the

postgenomicists of asthma& even as their efforts and kno3ledges are s3amped b the sublimit of

asthmas causes and e4acerbators+ " admire that the& like so man other postgenomicists& have

net3orked themselves into consortia that share data& results& materials& analtic techni;ues 00 as

3ell as their misgivings and uncertainties about all of these+ And " particularl admire ho3 the&

like so man other postgenomicists& have transvalued even the 9boring 3ork of curating and

caring for materialsLdata sets& materialsLdata banks& and materialsLdata techni;ues 5see e+g+

Beonelli and Anken )$#)8 so that these infrastructural activities have their o3n re3ards& virtues&

recognitions& and even surprises and interests far beond 3hat an dreamer of genomic futures

had in the #,%$s+

The Ama=ement of 24perimental Sstems and the Public Sphere

22


23/28

To revisit and re0sound m opening stor: " 3ant 9Toll? the e4pression& like toll the

gene& to register multiple effects in multiple signaling path3as& altered b multiple contingencies

of conte4t I environmental& temporal& developmental+ 9Weird? and 9.ool? are onl the first

t3o dominant registers probed b the translators of 'usslein01olhards speech act+ We should

add 9.ra=?& as cued b '/sslein01olhard herself 3hen& in another intervie3 for a popular

3ebsite& she reflected on a more meta0scientific level:

"ntervie3er: @at es in "hrem Beben den @eureka0Moment gegeben .#ave you ever hada /ure(a! oent in your life0

'/sslein01olhard: "mmer 3ieder mal+ Das ist gan= toll? .Again and again% That"s what"s so cra$y!0 . uoted in Weissmann )$$,:)#-8

To continue 3ith the dissemination of 9Toll?& to follo3 its dehiscent branchings do3n

the signaling path3as of semiosis& another orienting cue comes from 1A/& 2ournal editor0in0

chief Gerald Weissmann 3ho& in his o3n rumination on '/sslein01olhards 3ork and its affinities

to Gestalt pscholog& also invoked the comple4 net3ork of meanings activated b 9Toll?:

WQords shouted in the heat of discover have more than their dictionar meaning+ MemigreX father used 9toll 3hen he meant 9cra=& but also 9curious or 9ama=ingK heused it 3hen he first treated a patient 3ith cortisone+ These das German0speakers alsouse toll instead of 9cool or 9droll& 9outrageous or 9a3esome+ 5Weissmann

)$$,:)#%8

The entr of 9droll into our path3as here is rather unheilich& and reminds us of the capacit

of these sorts of disseminator informational net3orks to flip over into an opposite effect+

Something ver similar 3as registered in another on0line discussion tring to parse '/sslein0

1olhards outburst& 3here an initial ;uer at ask+metafilter+com ;uestioned @ansson and 2dfeldts

translation 5cited above8 of 9Das 3ar >a toll? as 9That 3as 3eird?:

" thought the translation 3ould be that 3as ama=ing? 5unless spoken sarcasticall&3hich " think can be ruled out8 or that 3as cra=?J Does anbod kno3 3here thisanecdote comes from "Rve searched through the 3eb 5although not e4haustivel8& but tono avail :05

The possibilit of sarcasm 3hich this initial ;uerier ruled out 3as ;uickl ruled back in b

another respondent:

23


24/28

" lived in German for a total of five ears+ "Rve never used the 3ord toll 5or heard the

3ord used& for that matter8 to mean 3eird or odd+ .ool and A3esome are much

closer to the mark& though toll lends itself much better to sarcasm than either of its

2nglish e;uivalents& for some reason+ %

'o3& finall& " too am 9closer to the mark " aimed for 3ith this essa& and can condense

its claim to its most compressed form 3ithout too much risk of being read as reductionist:

3hereas genomics 3as ostly felt to be a boring machine tool& overcoded b the code discourse it

directed at genomes to straightfor3ardl translate or decode them& postgenomics is ostly felt to

be cool and a3esome and cra= and 3eird and droll and outrageous and I 9for some reasonC

not? Attending to affect offers a comple4 of surprises and interests& not a simplified

understanding of postgenomics+

9" couldnt see the path because the path 3asnt there& Manard ect+ This

vie3 of the entire histor of the @uman Genome Pro>ect can be read as a confirmator signal for

!heinbergers vie3 of e4perimental sstems as a ma=e:

An e4perimental sstem can be compared to a labrinth 3hose 3alls& in the course of

being erected& simultaneousl blind and guide the e4perimenter+ The construction

principle of a labrinth consists in that the e4isting 3alls limit the space and the directionof the 3alls to be added+ "t cannot be planned+ "t forces one to move b means of

checking out& of groping& of tat3nneent4The articulation& dislocation& and reorientation

of an e4perimental sstem appears to be governed b a movement that has been described

as a pla of possibilities .5eu des possibles0% With Derrida& 3e might also speak of a

9game of difference+ "t is precisel the characteristic of 9fall5ing8 pre to its o3n 3ork

that brings the scientific enterprise to 3hat Derrida calls 9the enterprise of

deconstruction+ 5!heinberger #,,%:),#8,

8 http:LLask+metafilter+comL%H7#7LWhat0can0Das03ar0>a0toll0meanK accessed ul )%&

)$##+


25/28

"n an age of austerit& it seems eas to forget& and eas to devalue& that postgenomics is a

game that provides its plaers 3ith a high degree of surprise and e4citementCtempered b

tedium+ Wh should 3e as a societ pa 5a lot?8 to boost their levels of interest0en>oment "m

mostl marking the ;uestion here& and ackno3ledging its difficult and its risks+ " am not

comfortable 3ith it& 3hich means that the ;uestion boosts m level of interest0en>oment& even as

it leaves me pre to m o3n 3ork& groping in the labrinth for a path that is al3as onl

emerging+

9And etJ

Genomics and postgenomics have received plent of hperenthusiastic adulation and

plent of deflationar criti;ue I both of 3hich& it bears stressing again& are 3ell 3arranted+ Eut

these rather one0dimensional alternatives need to be doubled& at least& read together and against

each other& if the are to do >ustice to the cra=& cool& a3esome& e4citing& boring& droll& and mad

pursuit of postgenomics+ As genomics shaded into postgenomics& it became more and more toll!

I and that surprised everone& including its chroniclers I at least this one+ Attending to toll0like

e4pressions of surprise and e4citement 3ill enrich our o3n stles of 9dnamic ob>ectivit in

historical and ethnographic analses of postgenomics& binding our o3n account to the fuller range

of the forces shaping this scientific field+ (es& postgenomicists can be seekers of profit& affirmers

of baseless 9racial categories& purveors of problematic personali=ed medicines& and all the other

personas implicit or e4plicit in so man ethical& legal and social studies of this ever emergent

ensemble of scientific practices+ Eut& as a necessar supplement to these necesssar accounts& 3e

could stand to come to better terms 3ith the surprise0seeking& creativit0affirming& e4citement0

purveing dimensions of postgenomicists personas I even& perhaps especiall& if those terms

include toll!0like amalgams+

and the Actual 5Seattle: Nniversit of Washington Press& #,%)8 does not conve thisconnotation from the French title& 6e 2eu ossibles8+ The Derrida ;uote is from 7f8raatology& trans+ Gaatri Spivak 5Ealtimore: ohn @opkins Press& #,-H& p)0)H+

25


26/28

" think there is also a politics to the pursuit of toll!0like affect in contemporar science

that is also a necessar supplement to the necessar politics of criti;ue+ There is a need in

American culture for a greater collective capacit for the surprise0startle and interest0en>oment

that comes through engagement 3ith comple4 scientific sstems& comple4 arguments& and

comple4 realities+ "n a time of austerit& compounded b a pervasive devaluation of man kinds

of kno3ledge spiked b elements of outright anti0scientism 5in the N+S+ at least8& re0reading a

genealog of postgenomics could contribute to a cultural need for ne3 idioms for a re0valued

science that e4tend beond its pragmatic applicabilit& to encompass its abilit to provoke

3idened& shared curiousit about comple4 biological& cultural& and environmental conditions+ M

e4perimental hope is that adding a comple4 toll!-like amalgam of affects to the diversit of

receptors through 3hich 3e make sense of postgenomics untimel course of continued

emergence 3ill produce& as it has for at least some postgenomicists& surprising effects driven b

and emboding of attentive care+

!2F2!2'.2S

Eelvin& Marcia P+& and 6athrn 1+ Anderson+ #,,7+ A .onserved Signaling Path3a: The Drosophila Toll0Dorsal Path3a+ Annual 9eview of Cell and Developental &iology #):,0H#7+

.ollins& Francis+ )$#$+ A genome stor: #$th anniversar commentar+ Scientific Americanonline& une )+

2d3ards& Paul+ )$#$+ A :ast Machine+ M"T Press+

Fortun& Mike+ )$$%+ roising 8enoics;


27/28

Fu>imura& oan& and !ama !a>agopalan+ )$##+ Different differences: The use of Ogeneticancestr versus race in biomedical human genetic research+ ocial tudies of cience H#58:0$+

Gilbert& Walter+ #,,#+ To3ards a paradigm shift in biolog+ Nature H,:,,+

6eller& 2veln Fo4+ #,%+ 9Dnamic ectivit: Bove& Po3er& and 6no3ledge+ 9eflections on8ender and cience% 'e3 @aven: (ale Nniversit Press+

000 #,,7+ =Drosophila 2mbros as Transitional ects& #istorica> tudies in the hysical and &iological ciences 75)8:#0H7+

#,,-+ Developmental biolog as a feminist cause 7siris& )nd series& vol #):#70)%+

Beonelli& Sabin& and !achel Anken+ )$#)+ !e0thinking organisms: The impact of databases on

model organism biolog+ tudies in the #istory and hilosophy of &iological and &ioedical

ciences H:),07+

'elson& 6aren 2+& and Eran A+ White+ )$#$+ 9Metagneomics and its application to the stud ofthe human microbiome+ Pp+ #-#0#%) in Marco& Diana 5ed+8& Metagenomics: Theor& Methods&and Applications+ 'or3ich: @ori=on Scientific Press+

'e3 (ork Times+ )$#$+ The Genome& #$ (ears Bater+ une )$+

Patton& Paul+ )$$,+ 2vents& Eecoming& and @istor+ Pp+ 0 Deleu=e and @istor+ effre A+ Eell

and .laire .olebrook& eds+ 2dinburgh: 2dinburgh Nniversit Press+

!heinberger& @ans0Yrg+ 924perimental Sstems& Graphematic Spaces+ "nscribing Science:

Scientific Te4ts and the Materialit of .ommunication& ed+ Timoth Benoir+ Stanford #,,%+

!ice& .linton& ugal 6+ Ghorai& 6athrn Vale3ski& and Daniel '+ Weber+ )$##+

Developmental lead e4posure causes startle response deficits in =ebrafish+ A?uatic

To)icology #$ 50H8:7$$07$%+ doi:10.1016/j.aquatox.2011.08.014

Sedg3ick& 2ve 6osofsk& and Adam Frank+ 9"ntroduction+ The Silvan Tomkins !eader+

Stengers& "sabelle+ )$#$+ 24perimenting 3ith What is hilosophy "n Deleu$ian

etil

!od>e+ 'e3 (ork: Eerghahn Eooks+

Sternberg& !ichard+ )$$)+


28/28

N+S+ Senate+ #,,$+ The @uman Genome Pro>ect+ Subcommittee on 2nerg !esearch and

Development& .ommittee on 2nerg and 'atural !esources+ ul ##+ 5#$#st .ongress& #st

session& S+ @rg+ #$#0%,H8

Wade& 'icholas+ )$#$+ A Decade Bater& Genetic Map (ields Fe3 'e3 .ures+ New 'or( Ties,

une #)+

Watson& ames D+ )$$-+ Avoid &oring eople; 6essons 1ro a 6ife in cience+ 'e3 (ork:

6nopf+

0000 #,,$+ Address at Stated Meeting of the American Academ of Arts and Sciences& .ambridge&

Massachusetts& Februar #H+ Authors transcript+

Weissmann& Gerald+ )$#$+ Pattern !ecognition and Gestalt Pscholog: The Da 'usslein0

1olhard Shouted 9Toll? The 1A/& 2ournal @ 5ul8:)#-0)#H#+

Vimmer& .arl+ )$#$+ 9(et0Another0Genome Sndrome& April )Khttp:LLblogs+discovermaga=ine+comLloomL)$#$L$HL$)Let0another0genome0

sndromeLZ+N!V#3;tevEoK last accessed March #& )$#+
http://blogs.discovermagazine.com/loom/2010/04/02/yet-another-genome-syndrome/http://blogs.discovermagazine.com/loom/2010/04/02/yet-another-genome-syndrome/#.URZ1wqtevBohttp://blogs.discovermagazine.com/loom/2010/04/02/yet-another-genome-syndrome/#.URZ1wqtevBohttp://blogs.discovermagazine.com/loom/2010/04/02/yet-another-genome-syndrome/http://blogs.discovermagazine.com/loom/2010/04/02/yet-another-genome-syndrome/#.URZ1wqtevBohttp://blogs.discovermagazine.com/loom/2010/04/02/yet-another-genome-syndrome/#.URZ1wqtevBo

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