Fluoroquinolone Research Momentum Builds, Phase II In Preparation Fluoroquinolone DNA-Adduct Testing Project Results By Joseph King WARNIN !

"ou #$y %or&$rd this in%or#$tion' (ut it is prohi(ited to (e pu(lished (y $ny pu(lic$tion &ithout the per#ission o% the $uthor $nd rese$rch te$#) Rese$rch pu(lished o*er the l$st dec$de de#onstr$tes th$t Fluoroquinolone $nti(iotics possess the potenti$l to $dduct to hu#$n DNA $t (oth the cellul$r $nd #itochondri$ DNA le*els) Fluoroquinolone DNA-$dducts h$*e (een suspected $s $ potenti$l culprit in post+Fluoroquinolone illness' (ut no hu#$n Fluoroquinolone DNA-$dduct clinic$l studies h$*e (een conducted $nd pu(lished until no&) There%ore' o*er the p$st si, #onths -(eginning $t the end o% August ./012 discrete testing o% $ di*erse s$#pling o% indi*idu$ls de*$st$ted (y the Fluoroquinolone $nti(iotics &$s conducted) I &$s $s3ed to direct this rese$rch $nd coordin$te the in*estig$tion &ith $ te$# o% (ioche#ist' (iogenetic engineers' to,icologist' ph$r#$cologist' $nd #icro(iologist (oth n$tion$lly $nd intern$tion$lly) BA4K R56ND7 DNA $dducts $re che#ic$l co#pounds th$t $re (ound to one or #ore o% the $#ino $cid protein #olecules constructing the DNA o% li*ing org$nis#s) 5nce this e*ent occurs' th$t section o% the org$nis#s DNA $nd the section8s represent$ti*e gene is %r$ctured) The source o% the che#ic$l co#pounds th$t (ind $nd %r$cture DNA c$n (e either e,ogenous or endogenous $nd c$n $lso include #et$(olites -%r$g#ents2 o% che#ic$l #olecul$r structures) 5ther &ords' the entire co#pound' $ %r$g#ent o% the co#pound' or $ #et$(olite %or#ed %ro# the co#pound c$n $dduct to the DNA $#ino $cid structure i% there is $ #olecul$r $ttr$ction (et&een $ny o% the t&o) The Fluoroquinolones de#onstr$te such $ #olecul$r $ttr$ction) A DNA-$dduct &ill su(sequently (loc3 th$t corresponding gene8s e,pression $nd $(ility to replic$te correctly) This hinders th$t gene8s $(ility to encode $nd correctly o*ersee the production o% the protein synthesis necess$ry %or its $ssoci$ted cell $nd tissue regener$tion' replic$tion' $nd rep$ir) This is (etter 3no&n $s genoto,icity Along the entire DNA heli,' there $re sections th$t represent the genes th$t #$3eup th$t li*ing org$nis#) The 9u#$n eno#e Project h$s re*e$led th$t there $re $ppro,i#$tely ./'///-.:'/// genes section$li;ed $long our DNA) enes $re responsi(le %or e*ery $spect o% #$int$ining th$t org$nis# (y' $#ongst other %unctions' orchestr$ting the reproduction $nd rep$ir o% cells) 4ells th$t #$3eup the li*er' (r$in' ner*es' #uscles' connecti*e tissue' (ones' $nd $ll other org$ns o% the hu#$n (ody) 5ne #$jor role th$t genes pl$y is the encoding o% protein' t$3ing ingested protein $nd #$nu%$cturing ne& cells' li3e #uscle cells) But i% th$t gene is d$#$ged through $ DNA-$dduct' the (io-che#ic$l %or#ul$ held (y th$t gene -encoding2 %or #i,ing the protein correctly in the #$nu%$cturing

o% ne& cells -%or th$t org$n2 is %l$&ed' #ut$ted) I% this occurs' th$t org$n o% the (ody does not rep$ir or replenish itsel% correctly or ti#ely' $nd (egins to #$ni%est $ *$riety o% sy#pto#s' p$in' %$tigue' &$sting' $nd others) In nu#erous c$ses the (ody &ill respond to these %l$&ed cells $s $lien' $nd produce $nti(odies to $tt$c3 these cells $s $n $utoi##une response) This $utoi##une response c$n produce in%l$##$tion' p$in' de(ilit$tion' $nd $ddition$l he$lth $nd physic$l ch$llenges) Tod$y the #ost e%%icient $nd e,$cting testing %or co#pounds $dducting to DNA is the use o% 9igh Per%or#$nce <iquid 4hro#$togr$phy+T$nde# =$ss >pectro#etry -9P<4-=>?=>2) A t$nde# #$ss spectro#eter is $ speci$li;ed instru#ent th$t detects che#ic$l co#pounds (y #e$suring their #olecul$r &eight -#$ss2) =$ss spectro#eters deter#ines $nd qu$nti%ies the &eight o% the #olecules -9ydrogen' 5,ygen' 4$r(on' etc)2 co#prising $ che#ic$l co#pound electronic$lly' $nd produces $ spectrogr$# displ$ying the e,$ct &eights o% e$ch seg#ent o% the co#pound' this is 3no&n $s $ #$ss spectru#-spectrogr$#) This is $ highly $ccur$te $nd speci%ic $n$lysis since e$ch che#ic$l structure ret$ins its o&n unique #olecul$r &eight %or#ed %ro# its unique $to#ic structure) Addition$l *eri%ic$tion is pro*ided through the instru#ent (y pro*iding the indi*idu$l #olecul$r #$ss -&eights2 o% the seg#ents -%r$g#ents2 o% #olecules -$to#s2 $rr$nged to produce the che#ic$l co#pound) In essence' T$nde# =$ss >pectro#etry re*e$ls the co#pound' the group o% #olecules $rr$nged to #$3e the co#pound' $nd structur$l in%or#$tion $t the #olecul$r le*el surrounding the co#pound under in*estig$tion) Thin3 o% it $s re*e$ling the %orest' the $rr$nge#ent o% the trees' the grouping o% the trees' $nd the type o% trees in e$ch o% the groups producing the %orest) T@>TIN R@>6<T>7

This testing co##enced in l$te August ./01) An$lysis h$s (een ongoing to d$te' $nd &ill continue throughout ./0A) Fi*e indi*idu$ls &ere selected th$t h$d (een dosed &ith $ Fluoroquinolone -FB2 $nti(iotics! pri#$rily 4ipro%lo,$cin -4ipro2 or <e*o%lo,$cin -<e*$quin2 ) @$ch p$rticip$nt &$s selected ($sed upon dur$tion o% dosing $nd currently reported #edic$l conditions th$t did not pre-e,ist prior to $d#inistering the $nti(iotic) To (e included in the study' p$rticip$nts h$d to (e e,posed to $ %luoroquinolone $t le$st three ye$rs prior) This ti#e %r$#e &$s est$(lished to ensure th$t seru# circul$ting le*els o% FBs &ould (e dissip$ted %ro# (lood s$#ples $s indic$ted (y the drug #$nu%$cturers) All indi*idu$ls &ere *olunt$ry p$rticip$nts in this study) Three %e#$les $nd t&o #$les &here selected) De#ogr$phics o% p$rticip$nts *$ried %ro# n$tion$l $nd intern$tion$l loc$tions) 5ccup$tion$l ($c3grounds gre$tly *$ried' (ut &here li#ited to pro%ession$l e#ploy#ent $nd there(y $(sent o% $ny h$;$rdous or industri$l #$teri$ls e,posure or che#ic$l to,ins)

P$rticip$nt Age Anti(iotic Dosing =$le AC 4PD ://#g , . =$le :/ <ED ://#g , . Fe#$le :0 4PD?<ED ://#g , . Fe#$le 1G <ED C:/#g , 0 Fe#$le A. 4PD ://#g , . H 4ipro%lo,$cin -4PD2' <e*o%lo,$cin -<ED2I

Dur$tion A. d$ys C d$ys 1/ d$ys 0 d$y C d$ys

"e$r ./0/ ./0/ .//F ./0/ ./0/

5ccup$tion Pro%ession$l Pro%ession$l Rese$rcher Pro%ession$l 4onsult$ncy

All %i*e p$rticip$nts reported good he$lth prior to ingesting FBs' &ere physic$lly %it' $cti*e' cogniti*e' non-sedent$ry' $nd non-recre$tion$l drug users) All %i*e de#onstr$ted e,tensi*e genetic d$#$ge $s deter#ined (y gene-sequencing $n$lysis $nd *$ried chronic he$lth conditions th$t did not e,ist prior to dosing) Di$gnosed 9e$lth 4onditions o% p$rticip$nts $%ter Fluoroquinolone tre$t#ent P$rticip$nt-Age-4hronic 9e$lth 4onditions =$le -AC2 Neurop$thy' cognitive disturbances, sensory disturbances,
gastrointestinal issues, cardiovascular disturbances and skin reactions'

(ody p$in' $nd %$tigue =$le -:/2 Neurop$thy' chronic (ody p$in' joint p$in' %$tigue' g$stro-intestin$l intoler$nces' $nd di#inished cognition Fe#$le -:02 Neurop$thy' connecti*e tissue destruction' #uscle &$sting' chronic (ody p$in' joint $nd #uscle p$in' chronic %$tigue' di#inished cognition' electro#$gnetic r$di$tion intoler$nce' chronic respir$tory pro(le#s' %ood $llergies' $nd en*iron#ent$l $llergies Fe#$le -1G2 Neurop$thy' chronic (ody p$in' joint $nd #uscle p$in' %$tigue' di#inished cognition' electro-#$gnetic r$di$tion intoler$nce' chronic respir$tory pro(le#s' %ood $llergies' $nd en*iron#ent$l $llergies Fe#$le -A.2 Neurop$thy' chronic (ody p$in' di#inished cognition' electro#$gnetic r$di$tion intoler$nce' %$tigue' %ood $llergies' $nd en*iron#ent$l $llergies The control group &ere recruited %ro# intern$l l$(or$tory sources $nd included t&o indi*idu$ls &ho h$d ne*er (een e,posed to $ny type' cl$ss' or su(cl$ss o% $nti(iotics' drugs' en*iron#ent$l co#pounds' or to,ins' $s *eri%ied (y sel%-report $nd prescreened using $s 4hro#otogr$phy $n$lysis %or $ny to,ins -to,icity screening2' #edic$tions' $nd illeg$l drugs in (lood seru#' $nd h$ir s$#ples using st$nd$rdi;ed %orensic to,icology protocols)

0/ #illiliters o% &hole (lood &$s e,tr$cted *i$ *enipuncture into $ E$cu-Eile cont$ining $ st$nd$rd $ntico$gul$nt' $nd deli*ered (y o*ernight $ir-e,press to the testing l$(or$tory %or processing) >t$nd$rdi;ed shipping $nd h$ndling #ethods %or hu#$n (iologic$l %luids &$s i#ple#ented utili;ing $ 6nited N$tions $ppro*ed 6N-11C1 Biologic$l >u(st$nce Bo, $nd tr$nsport require#ents' the ch$in o% custody &$s #$int$ined during $ll st$ges o% collection' tr$nsport' $nd deli*ery) The l$( processed the (lood s$#ples (y sep$r$ting the pl$s#$ %ro# the red (lood cells -pl$telets2 (y centri%uging the (lood) The red (lood cells &here e,tr$cted $nd the protein #e#(r$ne o% the red (lood cells &$s re#o*ed utili;ing $ &idely $ppro*ed $nd recogni;ed che#ic$l chel$ting procedure $dopted (y to,icology l$(or$tories &orld&ide) This e,posed the cell DNA $nd =itochondri$ DNA' (oth loc$ted in hu#$n (lood cells) The re#$ins &here centri%uged $g$in sep$r$ting the t&o sources o% (lood cell DNA %ro# the protein #e#(ers' producing $ppro,i#$tely 0// #icrogr$#s o% DNA per s$#ple to (e e,tr$cted %or testing) ) A 9igh Per%or#$nce <iquid 4hro#$togr$phy T$nde# =$ss >pectro#eter -9P<4-=>?=>2 &$s utili;ed ($sed upon prior pu(lic$tions touting $nd supporting the role o% 9P<4-=>?=> $s the %uture &$*e in detecting DNA $dducts in to,icology $nd genetic studies) 6pon co#pletion o% the $n$lysis o% the %i*e indi*idu$l (lood DNA s$#ples' t&o control s$#ples &here prep$red $nd $lso $n$ly;ed) Results &here crossco#p$red to the %i*e e,posed (lood DNA s$#ples) All %i*e o% the Fluoroquinolone e,posed (lood-DNA s$#ples re*e$led the s$#e identic$l #$r3ers %or DNA-$dducts origin$ting %ro# Fluoroquinolone dosing) While the control s$#ples &here *oid o% the #$r3ers %ound in the Fluoroquinolone group) The control s$#ples re#$ined %l$t $cross the spectr$l spre$d &ith no signi%ic$nt #$r3ers re*e$ling $ny to,ins or Fluoroquinolones $s DNA $dducts) 9o&e*er' signi%ic$nt Fluoroquinolone #$r3ers &ere %ound &ithin the test group $s DNA-$dducts) Identi%ic$tion o% Fluoroquinolone #et$(olites $nd co#pound %r$g#ents &here $lso %ound $t ele*$ted le*els $s DNA-$dducts) It &$s re*e$led th$t (oth the Fluoroquinolone co#pound itsel% $nd #et$(olites %ro# the Fluoroquinolone co#pound &here $dducted to the DNA o% the test group) 45=P56ND> ID@NTIFI@D A> DNA-$dducts in T@>T R56P7

Fluoroquinolone $nd Buinolone =et$(olites %ound in test group using 9P<4T$nde# =>?=> R$n3ing (y pre*$lence7 4o#pound Re*e$led $s DNA-$dducts $s 4o#pound Fr$g#ents or =et$(olites o% Interest Re*e$led $s DNA-$dducts %ro# $n$lysis H 4ipro%lo,$cin -4PD2 $nd <e*o%lo,$cin -<ED2 I

0 Buinoline! ph$r#$-core o% $ll Buinolone ($sed $nti(iotics -heterocyclic core %r$g#ent o% 4PD $nd <ED2 . 4PD $nd <ED Residue' non-#et$(oli;ed $ccu#ul$ted residue o% the entire co#pound' tot$lity-int$ct 1 =ethyl Piper$;in! Piper$;in co#pound $tt$ched to Buinoline core co#pound o% 4PD $nd <ED A 0-4yclopropyl! 4yclopropyl $tt$ched to Buinoline core co#pound o% 4PD

: 1-4$r(o,ylic Acid! 4$r(o,ylic Acid $tt$ched to Buinoline core co#pound o% 4PD J <ED C G 4$r(o,ylic Acid! 4$r(o,ylic Acid $tt$ched to Buinoline core co#pound o% Buino;oline! =et$(olite o% Buinolone $nd Buinoline Anthr$quinone! =et$(olite o% Buinolone

The %ollo&ing gene #ut$tions $nd %r$ctures &here %ound in the %ollo&ing %i*e indi*idu$ls $s results %ro# the Fluoroquinolone DNA-$dducts 0 4"P - 4ytochro#e PA:/ %$#ily $nd su(groups Responsi(le %or the #et$(olis# o% #$ny drugs $nd en*iron#ent$l che#ic$ls th$t it o,idi;es $nd neutr$li;es . NAT - N-$cetyltr$ns%er$se NAT0' NAT. The NAT $cetyl$tion poly#orphis# is i#port$nt (ec$use o% its pri#$ry role in the $cti*$tion $nd?or de$cti*$tion o% #$ny che#ic$ls in the (ody8s en*iron#ent' including those produced (y cig$rettes $s &ell $s $ro#$tic $#ine $nd hydr$;ine drugs used #edicin$lly) In turn' this c$n $%%ect $n indi*idu$l8c$ncer ris3) 1 AD - lut$#ic Acid Dec$r(o,yl$se' Neurop$thy $nd >ti%%-Persons->yndro#e AD0

A =T9FR Protein-4 de%iciency resulting in l$ter-onset neurodegener$ti*e disorders : PRTN' PRTN1' PR-1 Protein$se?Protein$se-1Poly#orphonucle$r leu3ocyte serine prote$se th$t degr$des el$stin' %i(ronectin' l$#inin' *itronectin' $nd coll$gen types I' III' $nd IE Hconnecti*e tissue - #uscul$r?s3elet$l co#plic$tionsI

J 45=T - 4$techol-5-#ethyltr$ns%er$se 4$t$ly;es the tr$ns%er o% $ #ethyl group %ro# >-$denosyl#ethionine to c$techol$#ines' including the neurotr$ns#itters dop$#ine' epinephrine' $nd norepinephrine) C =A5 4$t$ly;es the o,id$ti*e de$#in$tion o% (iogenic $nd ,eno(iotic $#ines $nd h$s i#port$nt %unctions in the #et$(olis# o% neuro$cti*e $nd *$so$cti*e $#ines in the centr$l ner*ous syste# $nd peripher$l tissues With $n esc$l$ting nu#(er o% indi*idu$ls th$t h$*e (een dosed &ith $n Fluoroquinolone reporting de(ilit$ting re$ctions to the tre$t#ent' &e #ust consider th$t $ serious (ioche#istry $lter$tion is #$ni%esting &ithin these *icti#s) A (ioche#ic$l ch$nge th$t h$s resulted in genetic d$#$ge re*e$led through geno#e sequencing testing (y FB *icti#s post tre$t#ent) 5ngoing testing h$s sho&n speci%ic gene %r$ctures $nd #ut$tions repe$tedly $#ongst thous$nds o% p$rticip$nts dosed &ith $n FB) >uch genetic d$#$ge c$n only result %ro# one o% %our sources! 0) 9eredit$ry-Inherited - $ gene #ut$tion p$ssed %ro# p$rent to child) This c$tegory &ould gener$lly sho& sy#pto#s &ithin the e$rly ye$rs o% the child8s gro&th $nd de*elop#ent) This h$s not (een the c$se in FB respondents' no prior or pre-e,isting conditions o% this origin h$*e (een reported' $nd cert$inly not (y the test group .2) R$di$tion e,posure' pri#$rily %ro# nucle$r %$llout) Ag$in' this h$s not (een the situ$tion in*ol*ing the FB respondents or the test group $s their source o% genetic d$#$ge 12) @n*iron#ent$l to,ins could (e considered) 9o&e*er' FCK o% the FB *icti#s sho&ing genetic d$#$ge h$*e reported th$t they h$*e ne*er (een e,posed or &or3ed in $n en*iron#ent conduci*e to to,ins o% $ny c$tegory A2) Directly ingested to,ins o% $ concentr$tion $nd dur$tion signi%ic$nt enough to $lter the indi*idu$l8s DNA per#$nently in the %or# o% $ DNA $dduct) There h$s (een only one co##on %$ctor reported $nd %ound $#ong the Fluoroquinolone *icti#s $nd the study group' $ Fluoroquinolone $nti(iotic) This singul$r co#pound h$s (een the only thre$d lin3ing these indi*idu$ls to the dec$y in their he$lth' genoto,icity' genetic #ut$tions' de*eloped $nti(odies' $nd the DNA $dducts disco*ered in the test group) DNA-$dducts $re nothing ne&) The process h$s (een rese$rched $nd tr$c3ed %or dec$des) A DNA-$dduct is $ny co#pound th$t #olecul$rly $rr$nges itsel% to cle$*e to one or #ore o% the %our $#ino $cids th$t construct the DNA o% li*ing

org$nis#s) 5nce this e*ent occurs th$t section o% the org$nis#s DNA $nd the section8s represent$ti*e gene is %r$ctured) This hinders th$t speci%ic gene8s $(ility to encode $nd correctly o*ersee the production o% the protein synthesis necess$ry %or corresponding tissue regener$tion $nd replic$tion) This is (etter 3no&n $s genoto,icity) Prior to this project it &$s o% gener$l consensus th$t DNA-$dducts origin$ted pri#$rily %ro# en*iron#ent$l to,ins -posions2' such $s Ben;opyrenes' he$*y #et$ls' DDT $nd co#pounds o% si#il$r #olecul$r structures) 9o&e*er' on going rese$rch surrounding the co#pound .-A#ino-1'G-di#ethyli#id$;o A':-% Lquino,$line (etter 3no&n $s =elB, $nd its sister =elB $s $ DNA-$dduct c$ught our $ttention &hen in*estig$ting the Fluoroquinolones) =elB, $nd =elB $re co#pounds th$t %or# &hen #e$t' especi$lly red #e$t is coo3ed $t high te#per$tures' $nd $dducts to #$##$li$n DNA) These co#pounds h$*e $ si#il$r quinoline-quinolone heterocyclic core structure to the FBs) This opened $ door o% in*estig$tion surrounding the recepti*eness o% $ quinoline-quinolone ($sed co#pound to position itsel% $s $ potenti$l DNA$dduct) This could $lso (e the c$se &ith che#other$py $gents th$t $re ($sed upon $ quinoline-quinolone core constituent) There is no dou(t th$t the quinolone #olecul$r core is $ *ery #$nipul$ti*e structure th$t per#its the construction o% po&er%ul che#ic$l co#pounds (oth industri$l $nd ph$r#$ceutic$l) 6n%ortun$tely it $lso $ *ery resilient co#pound th$t resists %r$g#ent$tion $nd re*ers$l) It $lso &orth noting th$t Fluoroquinolone $dducts or its #et$(olites %urther enh$nce the de*elop#ent $nd positi*e testing o% *$ried $nti(odies $g$inst $ltered cellul$r $cti*ity) >uch $nti(odies $s the $nglioside =0' D0(' $nd B0( th$t $re $ssoci$ted &ith neurologic$l sy#pto#s' neurop$thies' $nd neurodegener$tion) Also $nti(odies such $s Protein$se-PR1 th$t $re lin3ed to *$rious degener$ti*e connecti*e tissue dise$se) 5ther $nti(odies include >jogren' Rheu#$toid %$ctors' <upus' @pstein-B$rr $nd *$rious $nti-nucle$r $nti(odies) In the e*ent th$t the Fluoroquinolone co#pound h$s in%lected e,tensi*e genetic d$#$ge %ro# &idespre$d DNA-$dducts $cross the DNA heli,' *$rious hy(rid he$lth conditions #$y $ppe$r such $s! non-inherited =$r%$n8s >yndro#e' or N$3$jo-Nis3i#ur$ >yndro#e' (oth o% &hich $re on the incre$se glo($lly' $nd $re cl$ssi%ied $s #uscle-s3elet$l $lter$tions &ith connecti*e tissue destruction) These t&o syndro#es $re di%%icult to di$gnose $nd tre$t using current di$gnostictre$t#ent regi#ents $s (yproducts o% Fluoroquinolone DNA $dduction) Fluoroquinolones $nd enoto,icity7 9$s $ =onster Been 4re$tedM

9$s this cl$ss o% $nti(iotics cre$ted $ long ter# genoto,icity &ith %uture gener$tion$l pro(le#sM 4$n the e,ponenti$l up-tic3 o% neurologic$l' #uscul$r-

s3elet$l' $nd ph$nto# he$lth pro(le#s (e $ssoci$ted to these $nti(ioticsM "es' it is highly suspected' $nd current d$t$ $nd results $re pointing $n $ccusing %inger $t the Fluoroquinolones) It is ti#e %or the initi$tion o% $n intern$tion$l rese$rch response to this r$pidly gro&ing pro(le#) It is Ti#e %or Doctors to rethin3 their $ppro$ch to FB *icti#s) Doctors #ust underst$nd th$t $ p$tient &ith $ FB DNA-$dduct is not h$*ing $n ADR -$d*erse drug re$ction2 to the FBs) The p$tient h$s (een poisoned' cellul$r d$#$ge h$s occurred in response to $ to,ic re$ction) The p$tients origin$l genetic pro%ile h$s (een $ltered-#ut$ted' $nd their sy#pto#s $nd he$lth co#pl$ints $re not psychoso#$tic) But $re in %$ct legiti#$te he$lth concerns requiring tre$t#ents th$t &ill not $cer($te the condition or prop$g$te the genetic d$#$ge) It is going to (e the physici$nNs responsi(ility to reconstruct the (iologic$l cri#e $s $ #edic$l >herloc3 9ol#es to deter#ine the e,tent o% the genoto,icity $nd cellul$r d$#$ge c$used (y the FBs in their p$tients) The in*estig$tion (y the physici$n c$n e$sily (egin (y si#ply $s3ing the p$tient i% they h$*e e*er (een prescri(ed $ FB $nti(iotic) An 6rgent 4$ll %or Ph$se II Testing $nd Funding While there is $l&$ys $ pl$ce %or Oso%tO science consisting o% sur*eys $nd p$tient tr$c3ing' the ti#e is no& %or intensi*e testing o% those su%%ering %ro# these $nti(iotics) B$sed upon the e*idence th$t the %i*e indi*idu$ls tested only h$d one %$ctor in co##on' dosed &ith $ Fluoroquinolone $nti(iotic' $nd identic$l #$r3ers %or DNA $dduction (y these $nti(iotics &here %orthco#ing %ro# the $n$lysis' &e $re pro#pted to c$ll %or $ Ph$se II series o% testing) Ph$se II %unding $nd testing' &hether %ro# pu(lic or pri*$te %unding' &ould esc$l$te the rese$rch to include indi*idu$ls e%%ected (y the Fluoroquinolones in the e$rly ./// $nd 0FF/8s er$) This &ould cert$inly include #ilit$ry personnel di$gnosed &ith ul% W$r >yndro#e %ro# the 0FF/ to 0FF1 ti#e %r$#e) Kno&ing no& th$t soldiers deployed to the ul% W$r &here $d#inistered 4ipro%lo,$cin $s $ prophyl$ctic to (iologic$l &e$pons' they should (e included in the ne,t study) It is distur(ing th$t DNA-$dduct testing on these indi*idu$ls h$s ne*er (een conducted) We #ust $lso consider $ll the go*ern#ent $nd pri*$te &or3ers th$t &here de(ilit$ted $%ter (eing dosed &ith 4ipro%lo,$cin in .//0 $nd .//. in response to Anthr$, t$inted letters) Pri*$te %unding %or Ph$se II &ould (e ide$l since o*ersight could (e (etter $nd #ore rigidly i#ple#ented through independent non-drug #$nu%$cturer rel$ted #oder$tors &ith 3no&ledge in Fluoroquinolone to,icity) Fin$l Word7 <et #e e,tend #y deepest $nd he$rt%elt $ppreci$tions $nd respect to the te$# $nd %in$nci$l ($c3ers th$t l$unched this rese$rch) They s$cri%iced $ lot to eng$ged this rese$rch) Their dedic$tion $nd #oti*$tion to e,pose the d$#$ge %ro# the Fluoroquinolone $nti(iotics deser*es $ll our gr$titude $nd respect) Also'

$ gre$t $ppreci$tion to the scientist th$t guided the process $nd protocols) We $re inde(ted to $ll o% these indi*idu$ls) Respect%ully $nd gr$ciously' Joseph King)