transcript – saying genome to cancer with david … · transcript – saying genome to cancer...

© The Bulletproof Executive 2013

Transcript – Saying GeNOme to Cancer with David Haussler - #342

Bulletproof Radio David Haussler #342

2

Warning and Disclaimer

The statements in this report have not been evaluated by the FDA (U.S. Food & Drug Administration). Information provided here and products sold on bulletproofexec.com and/or upgradedself.com and/or betterbabybook.com are not intended to diagnose, treat, cure, or prevent any disease. The information provided by these sites and/or by this report is not a substitute for a face-to-face consultation with your physician, and should not be construed as medical advice of any sort. It is a list of resources for further self-research and work with your physician. We certify that at least one statement on the above-mentioned web sites and/or in this report is wrong. By using any of this information, or reading it, you are accepting responsibility for your own health and health decisions and expressly release The Bulletproof Executive and its employees, partners, and vendors from from any and all liability whatsoever, including that arising from negligence. Do not run with scissors. Hot drinks may be hot and burn you.

If you do not agree to the above conditions, please do not read further and delete this document.


3

Dave: Doyoufeellikeyou'restuckinlife?Likeyourcreativity'sblocked?YouneedtocheckouttheUnmistakableCreativePodcast.ThinkTedTalksandOprahputtogetheronapodcastshow.Theyrecentlytalkedabouttheartofstrategicgiftingandhowyoucanmakesomeonefeelappreciatedwithasimplegift.Tolistenandbecreativelyinspired,gotopodcastone.comordownloadthefreemobileappnow.

Speaker2: BulletproofRadio,astateofhighperformance.

Dave: You'relisteningtoBulletproofRadiowithDaveAsprey.Today'scoolfactofthedayisthatthereareabout37trillioncellsinthehumanbodyandifyouunwoundalloftheDNAencasedineachcellandputitendtoend,youwouldhaveenoughDNAtostretchfromthesuntoPlutoandbackseventeentimes.Thatisactuallykindofprofound.It'salsototally,totallynottruebecausetheorbitofPlutoisnotcircular,incaseyou'reintoastronomy,butanyway,it'sagoodanalogy.That'saboutright,ifyoulookattheaverageorbitofPluto,solet'sjustbeprecisehere.

BeforeIgetintotheshowtoday,whichImighthavejusthintedhassomethingtodowithDNA,ifyou'rearegularlistenerofBulletproofRadio,you'veheardmesharethetoptenlistofbiohacks.Let'stalkaboutnumbernine,FunHacksfortheBulletproofMind.Itmaysoundweirdbuthangingupsidedownisagreatwaytohackyourbrain.Regularlyinvertingtrainsyourbraincapillaries,makingthemstrongerandmorecapableofbringingoxygentoyourbrain.It'saprettystraightforwardthing.Moreoxygentothebrainmeansbetterperformanceforyou.

IgetmydailystretchandagooddoseofbrainoxygenwithmyTeeterInversionTable,whichisessentialforoptimumfocus,concentration,andmentalenergy.Italsojustfeelsgoodandit'saneffectivewaytokeepyourbackingoodshape.Thatfullbodystretchelongatesyourspineandtakesthepressureoffthediscssotheycanplumpbackup.Lesspressuremeansmoreflexibilityandlesspain.Ifyouhavebackpain,evenifyou'vebeenluckyenoughtoavoidit,youneedaTeetertoinverteverydaytokeepyourbackandyourjointsandyourbrainfeelinggreat.

Forover35years,Teeterhassetthestandardforqualityinversionequipmentyoucantrust,andthere'sanamazingofferjustforBulletprooflisteners.ForalimitedtimeyoucangettheTeeterInversionTable,thesameonethatIusewithbonusaccessoriesandafreepairofgravitybootssoyoucaninvertathomeortakethebootswithyoutothegym.Togetthedeal,whichisasavingsofover$138,youhavetogotogetteeter.com/bulletproof.Youalsogetfreeshippinganda60daymoneybackguaranteeandfreereturnssothere'sabsolutelynorisktotryitout.Remember,youcanonlygettheTeeterwithbonusaccessoriesandafreepairofgravitybootsbygoingtogetteeter.com/bulletproof.That'sG-E-T-T-E-E-T-E-R.com/bulletproof.Checkitout.

Ifyoudon'tknowabouttheBulletproofPerformanceKits,that'sprobablybecauseyouhaven'tbeentotheBulletproofStoreinalittlewhile.Ifyou'renewtoBulletprooforyou'rejustlookingtofigureoutwhatworksforotherpeople,we'vegotabunchofnewperformancekits.Morethanadozenofthemtochoosefromlikethecoffeekit,thebrainkit,thedetoxkitsandthesearebasedonwhattheBulletproofambassadorsdothathelpsthemperformbetter.Headon


4

overtobulletproof.comandcheckouthowyoucanpairtheseproductsuptogetmoreperformanceoutofyourbraineverysingleday.

Today'sguyisaguyI'mreallylookingforwardtohavingontheshowandyoumaynothaveheardofhimbeforebuthe'sdonesomeprettyamazingwork.He'salsoalittlebitdiverse.Heactuallystudiedpsychotherapyforalittlewhilebackinthedayandtodayhe'sadistinguishedprofessorofbiomolecularengineeringatUniversityofCalifornia,SantaCruz.He'salsoabioinformaticiancombiningmath,computerscienceandmolecularbiologytodevelopnewalgorithmstounderstandthehumangenome.He'sprettywell-knownifyou'reageneticsfocusedperson,forhisworkonthehumangenomeprojectwhereitwashisteamthatmadethefirstpubliclyavailablecomputationalassemblyofahumangenomesequenceontheinternet.HisnameisProfessor,Doctor,it'snotright.Anyways,hisnameisDr.DavidHaussler.

David: [Inaudible00:04:18]theprofessorsandthedoctors.It'swonderfultobehere.It'sgreattohaveachancetotalkwithyouabouttheexcitingpotentialforDNA.WecanprobablyuseitforotherthingsthanreachingtoPlutoandback.Ithinktheanalogythoughis[out00:04:39].Thereisanenormousamountofinformationinourgenomeandwe'rejustnowbeginningtounderstandit.

Dave: Iwasintriguedatyourveryearlyworkwiththehumangenome.BackinmycareerinSiliconValleyIranthewebandinternetengineeringprogramforUCSantaCruz,theextensionofSiliconValley.Iusedtoteachworkingengineershowtheinternetworkinsteadofhowcomputerspre-internetwork.It'sthefirstwaveofeCommercecompanies.Google'sfirstserverisonourdatacenters.WealsohadacompanycalledDoubleTwist.Ididworkontheirinfrastructure.Youknowwhotheseguysare,right?

David: DoubleTwist,yeah.

Dave: LiterallyI'vebeeninthedatacenterDoubleTwistforpeoplelisteningwasthecompanythatheldthedataasIunderstanditfortheworkyouweredoing,computationalanalysisandtheyweredoingthestorageforthehumangenome.ItwasawholefloorofadatacenterinAlameda,ifIrememberright.Ididarchitectureforthem.

David: DoubleTwistwasoneoftheearlybioinformaticscompaniesintheupsurgeleadinguptothecombinationofthehumangenomeprojectintheyear2000.Theywerebuiltbytheventurecapitalcommunityinviewthathere'sanopportunityanditsurelytoworkoutbutIthinkbeingconceivedandcreatedbytheventurecapitalistratherthananindependentgeniuswhoreallyhadapassionforit,theyweredoomed,Ithoughttheyweredoomedtofailurefromthebeginning.Youcan'tcreatethesecompaniesoutofwholecloth.Yougottohaveindividualsthatarepassionateabout...

Dave: YouneedyourCraigVenter.

David: Yeah,youneedsomebodylikeCraigoroneoftheothergreatthinkers.

Dave: Whoaretheothermaybelessfamousbutothergreatthinkersinthefieldthatyouwouldnametheothertwoorthreepeopleworthfollowing?


5

David: GeorgeChurch,EricLander,thereareanumberofreallyfascinatingpeopleinthisarea.I'llget

intotroubleifImakealonglistandleavesomebodyout.

Dave: Iunderstand,that'swhyIaskedfortwo.

David: TherearedozensanddozensandI'mjustgivingtheverybignamesthatareprobablyhousehold,somebodythat'sbeenon[Cobear00:07:00],thatlevel.Forinstance,Collins,Georgehavebeenonsoit'sagreatarea.Wedoexcitingthingsandwe'rethrilledtobeableto...

Dave: Oneofthethingsthatyoudothat'sparticularlyinterestingisyoufocusalotonhumangenomeandcancer.Talkalittlebitmoreaboutwhatyou'redoingtomapourgeneticpredispositionforcancer.Peoplelisteningmaynotknowalotaboutgeneticssogivemetheentrylevelviewbutalittledeeper.

David: Absolutely.ThequesttomapthehumangenomestartedoutearlyonwehadactuallyameetinghereatSantaCruz,thechancellorSinsheimercalleditin1985andhadsomeofthegreatexpertscomeandsay,"IsitpossibletomapthethreebilliondifferentbasesofAs,Cs,TsandGsinthehumangenome?"Figureoutwhatatypicalperson'sgenomelookslikebyhardcorebiochemistrytosequencethisanditwasinitiallythoughtthatthatwouldbeimpossiblebutitturnedoutthatby2000asyousaidwe'vehadthefirstdraftandwewereveryproudtodothecomputationalanalysis.

TherewereabunchoflittlesnippetsofDNAthatwereproducedbythegenomesequencingmachinesandwedidthekeyassemblytoputthemtogetherintoacoherentfirstdraftofourhumangenome.PostedthatontheinternetonJuly7th2000.ThiswassimultaneouswiththeproductionofthegenomebyCelerasoCraigVenter'scompanyandmygoodfriendandcolleagueGeneMyers.Wewenttoschooltogether.Ledtheassemblyofthatversionofthehumangenome.By2000,suddenlythereweretwoversionsofthehumangenomeandthatsetthestageforasubsequentdevelopmentinthinkingabout,"Okay,nowifthisistheoverallmapforthehumangenomeandwe'reall99.9%identicalattheDNAlevelthenwhataboutthedifferencesandhowdidthosedifferencesaffectourhealth?"

Theprimarydifferencesthatpeoplewerethinkingaboutintheinitialstageswerethedifferencesthatwehaveinourgenomesthatweinheritedfromourmomanddad.YougetonecopyofagenefrommomandonecopyofthegenefromdadandlittlevariationsinthosegenesintheDNAcanmakeadifferenceinyourhealthandinyourpropensitytogetvariousdiseases.Actually,thereisadisease,cancer,inwhichnewchangeshappenasyougrowolder.Notinthosetrillionsofcellsthatyouwerejustmentioninginthisintro,theyallstartessentiallywiththesamegenomethatyougotfrommomanddadbutasyougrowoldtheyaccumulatechangesandsowhencellsdividetheynaturallydon'tmakeaperfectcopyoftheirgenomeforthedaughtercells.

That'samainsourceofdifferencesbutalsoyoucanhavevariouschemicalsthatarecarcinogenicandincreasetheamountofmutationthatoccursinparticular,smokingcreatesthesecompoundsandtheycancausemutationsinthecellsinyourlungs.Somelightcancause


6

mutationsinthecellsofyourskinandthosearethensignificanteventsrarelydotheydoanythingbad,mostofthemmakenodifferencewhatsoeverbutwithtrillionsofcellstheoddsarethatifyoukeepgoingonlongenough,ifyoulivelongenoughthenyou'regoingtohaveabadcombinationofmutationsthatcausesthatcelltogrowintoacancertumor.

Wenowhaveconfirmedthroughcarefulinvestigationoverthelastfewdecadesthatcancerisactuallyverymuchageneticdisease.Thecauseofcancerismutationsthathappeninsomeofthecellsinyourbodythatcausethemtogorouge.TreatingcancerisallaboutkillingthecellsthathavethosedangerousmutationsanditisanenormouseffortandwearelearningsomuchmoreaboutitnowthatwecanreadtheDNAofthetumorcells.

Dave: I'mworkingonabookaboutmitochondriarightnow.I'mgoingprettydeeponkrebscycle.It'sabookmeantforlaypeopleandfranklyI'mnotauniversitygraderesearcheronmitochondrialbenchtopchemistrybutI'mprettygoodatwhatIdo.I'veinterviewedguyslikeDominicD'AgostinolookingatthemitochondrialangleoncancerandthemitochondrialDNAmutationswhichhappenmorequicklythanthehumangenomeDNA.

David: Nucleargenome.Thehumangenomehasanuclearcomponentinthemitochondrialgenome.

Dave: Thankyou.ThatisexactlywhatIwasthinking.YouhavethenuclearDNAwhichiswherewefocusallofthisandwe'redevelopingthisview,IamlookingatWallace'sresearchonmitochondrialepigeneticsandwhatgetsexpressedfromthenuclearsideofthings.I'mwondering,yourtakeonthis,youareoneofthetoppeopleintheworldlookingatthenuclearsideofgeneticsandcancerandI'mtalkingtootherpeoplewhoarelookingatthemitochondrialdysfunctionsideofcancer.Howdoyoulinethosetwoperspectivesup?Idon'tknow.

David: Ithinkmitochondriahavenowbeenshowntobeinvolvedinanumberofdiseasesincludingcancer.Theyareofcoursetheenergyfactoriesofthecellandsuch.Thatamongtheotherkeyrolestheyplayintellingacellwhetherit'sover,basically,youshouldcommitsuicideorwhetheryoushouldkeepgoing.Alloftheseinformationandenergyprocessesthatarerootedthroughthemitochondriaareimportanttothecellandimportanttodiseasesowecertainlyappreciatethevalueofthemitochondriaeventhoughithasatinygenome16,000basesofDNAcomparedtothethreebillionbasesofDNAinthenucleargenome.

Thenucleargenomecontainsmoreofwhatwearejustmorebitsofinformationaboutwhatwearebutthemitochondria,tinyasitisit'sveryimportantalsotoourhealth.Therearenumberofnewstudiesthatshowmitochondrialeffectsincancerandhowthatcanalterthecourseofthediseasebutagain,there'smoregoingoninthenuclearpartofthegenomeincancerthanthereisinthemitochondriaandthat'snotsurprisingjustbecausethere'ssomuchmorecomplexityinthenuclearpart.

Dave: Justgiventhesizethere.

David: Yes,justgiventhesize.

Dave: Howfararewefrombeingabletolookatsomeone'snuclearDNAandsaying,"Basedonthiswe


7

haveaveryreasonablelikelihoodofwhatkindofcanceryou'regoingtogetifyougetcancer"?

David: We'llnevergettothatpointwherewecanbehighlypredictivebecausetheprogressionofcancerdependsonrandomandinherentlyunpredictableevents.Itcouldbeacosmicraythatcomesdownandhitstherightplaceinthegenomeoftherightcellattherighttimeorwrongplacewrongtimeifyouwant.

Dave: Youcouldstartsmoking,right?

David: Yeah,youcanstartsmokingsowewon'tbeabletopredictitinthatsensebutIthinkthelargesthopeforthefutureisthatwewouldbeabletocatchitearlierthanwearenow.Themostdifficultproblemwithcancertodayisthatpatientsarecominginafterthecancerhasprogressedtoapointwhereit'sverydifficulttounwindandgetridofallthecancercells.Thehardestthingabouttreatingcanceristhatyouneedtogetridofallthecells.Ifyouleavesomebehindandtheygrowbackandthat'stheproblem.

Ontheotherhand,thegoodthingaboutcanceristhatyouonlyhavetokillthecells,youdon'thavetofixthem.Ifyouhavecellsthatyouneed,yourneuronsorsomethingandyou'retryingtoalterthemtoworkright,that'sverymuchharderthankillingcells.Thegoodpartofcancerisweonlyhavetokill,thebadpartiswehavetokillthemall.Therearechallenges.

Dave: There'sawholebunchofthingsIwanttoaskyoubasedonthat.I'velookedalotattherespirationofcells.Itseemsliketherearepre-cancercellsthatcanbefixedwhereyouhaven'tkickedoffthatcelldeathprocesscalledApoptosis.Doyouascribetothat?I'mnotacancerexpert.Youare,soI'maskingquestionswithoutmeaningtoquestionwhatyou'resayingthereortochallengewhatyou'resayingtherebutjusttogetanunderstanding.Iknowalotofpeoplewho'velistenedtotheshowhavehadheardseveralgueststalkingaboutincreasingelectronsinmitochondriaandreversinghypoxicstatesincellsandturninganaerobiccellsbackintoaerobiccellstherebypreventingthemfromfurtherprogressingtobecomecancerous.IstheremeatontheboneforthattheoryinyourexperienceorwasthismoreofanuclearDNAproblem?

David: Theredefinitelyisametabolicshiftthatoccursincanceranditdoestowardsanaerobicfromaerobic.Thatispartofthecancerswitchingintoametabolismthatisoptimizedfortumorgrowth.Cancerofcourseisanevolutionarystrugglewithinyourownbody.Thecancercellsarecompetingforrealestateagainstyournormalcells.Growingfasterandbeingmorevigorousinstealingresourceslikebloodvesselsarecharacteristicsofcancerbecausethat'scharacteristicofwhowinsthisbattleforrealestateinyourbody.Partofthatisshiftingmetabolismandthatbringsagaininthemitochondrialaspectbecausemitochondriaaresofundamentalinthismetabolicprocess.

Again,that'sjustpartofthestory.Theoverallcellcycleiscriticalandthat'sbeenthemostextensivelyinvestigatedincancer.Youhavetostartdividingandyou'dhavetodividealotandrapidlytobeabadanddangerouscancer.Whathappensisthatwhenyou'reanembryo,yourcellsaredividingalotandthenthatprocessslowsdownandsowhenyou'readult,mostofyourcellsaresenescent.Basicallytheyfinish,theyaredividingandtheyareoccupyingtheirplaceinyourbodyandtheyshouldn'tstartdividingagain.Whentheyreverttothis,"Wow,IthinkI'm


8

likeastemcelllikething,I'mgoingtodivideagain."That'sasymptomofcancerthatismorecentralandprofoundthantheenergyshiftbutit'sallpartofthestory.Therearemanyhallmarksofcancerthatwelookat.

Dave: Whatdoyoudoinyourlifetominimizeyourchancesofgettingcancer?

David: Itrytousesunscreen.Idon'tsmoke.IwatchsomeofthefoodsthatIeatsoyoudon'twanttoeatmoldypeanutsforexample.Aflatoxinisoneofthemostpotentcarcinogensknown.Therearenumberofchemicalcarcinogensthataren'tnecessarilyjustfromindustrialprocesses.Theyaresocalledorganic,naturalcarcinogenstheaflatoxingrowspeanutmoldgrowsifyou'reanorganicfarmerornot.Youcan'tjustsayIeatorganicandsoI'msafe.Youhavetobevery,verycognizantofthemoleculesthatyou'reexposedto,makesurethattheyarenotcancer-causing.

AsIsaidbefore,reallythemostimportantthingisdetectionandearlypreventionbecausenomatterhowcarefulyouare,there'sstillthisincreasingprobabilitythatyouwillhavethatunluckyeventthatwillcausemutationsinyourcellsasyougrowolder.Therearereallynoamountofdietandlifestylecanpreventthatriskbecauseit'sanintrinsicfactofthewaycellsdivideandhowtheyagethatwillforceustobeexposedtocancer.Infact,manyhavesaidthatthere'sadualrelationshipbetweencancerandlongevity.Wemayalterourmitochondrialifyou'reanNAD+personandsoforth.

Dave: Iam.

David: Alotofusaresowemayalterourlifestyleandevenourchemistrytolivelongerbutthatwillhavetheeffectofincreasingtheamountoftimethatourcellsarewaitingtomutate.Ultimately,yourchancesforcancerwilljustaccumulate.Ifwearegoingtobesuccessfulinveryhighlongevitysituationthenwewillhavetodobetterwithcancer.Itwon'tbedietthatwillsaveusfromcancer.It'sgoingtohavetobedetectionandpreventionandrapidtreatment.We'llneedthatmoreandmoreasweage.

Dave: Nodoubt,ifyoulivelongeryouhaveagreaterincidentsofcancer.

David: That'sit,yup.Nothingthatcanchangethatcompletely.

Dave: WhenwetalkaboutNAD+thereforlisteners,whenyourmitochondriaaremakingenergy,youaddelectronsNAD+andtheycouldendupNADHandwhat'sgoingonthereisifyoucanchangetheratioofthosetwomoleculesyoucanchangetheefficiencyofyourmitochondriaandtherebyhavemoreenergyrightnowwhichisoneofthebigtopicsofmyupcomingbook.Alsopotentiallychangeyourriskofthemitochondrialsideofcanceratleastthat'swhatsomeoftheresearchI'veseensays.ByimprovingtheefficiencyoftheKrebsCyclereducingoxidativespeciesinthecells,itappearstohaveacancer-reducingrisk.Forsomecompoundsitevenappearstomakechemotherapyworkbetter.

David: Chemotherapyisahellofatoxicthing.Alltheorganicfruitandsoforththatyou'reeatinghasalittleeffectcomparedtothedramaticeffectsofthechemotherapycompoundsthatarecommonlyusedtotreatcancerandradiationofcourseagainwhichisstillcommonlyusedto


9

treatcancer.OneofthegoalsofcancerresearchbasedonourknowledgeoftheDNAandtheDNAmutationsistotrytogetbeyondsomeofthesemoretoxicmethodsfortreatingcancer.Ifyou'refacedwithcancerthatissomuchmoreimportantthanthehealthydietortheNAD+.Itreallyisimportantthatwegettothepointwherewecanhavetherapiesthatareprecisiontargetedtowardsthecellsthathavecancerandhavelittlecollateraldamageontheothercells.

That'sbeenamajorgoalandit'samajorhope.TheVicePresidenthasannouncedthemoonshotandthere'soptimism.Alotofthisoptimismisbasedontheideathatmaybewecancoaxorinduceyourownimmunesystemtofightoffthecancercellsandthisisanideathat'sbeenaroundfordecadesbutonlybecomereallyoperationalwithinthelastfewyearsandhasresultedinsomespectacularresultsforcertaintypesofcancers.We'restilltryingtounderstandwhyitworksforthosecancersanddoesn'tseemtoworkforothercancersatleastintheincarnationweknowaboutthisimmuneapproachwesometimescallimmunotherapy.

Thatwouldobviouslybeaterrificapproachtocancerifyoucanjustgetyourownbodytoeliminatethecancerbytargetingyourimmunesystemtoit.That'sterrific.Partofthatincombination,alotofpeoplearetalkingaboutdoingthatincombinationwithcripplingorkillingmanyofthecancercells.Theimmunesystemisdrawnintoafightsometimesthatisstartedbyeitherchemotherapyorsomeotherkindoftargetedtherapyandiftheimmunesystemcanlockonandfinishthejob,thatisterrificincancer.

Dave: Theimmunotherapyyou'retalkingaboutthereactuallysavedmycousin'slife.IwishIknewexactlywhatkindofcanceritwas.Ibelieveitwasabrainthing,somekindofprettyaggressivething.ThisisnotacousinI'mcloseto.It'swife'sfamilyinEuropebutheflewtoIsraelanddidaveryadvancedformofimmunotherapywheretheyessentiallyinlayman'stermmadeavaccinetosomecancercells,injecteditandhe'sperfectlyhealthywithnosignsofcancertoday.Thiswouldn'thavehappenedfiveyearsago.It'sjustshocking.

David: No,itcouldn't.It'sspectacular.Thatformoftreatmentwhereyou'reactuallyusinganinactivatedvirusorsomethinglikethattodrawattentionoftheimmunesystemtothetumor.Youcandothiswithbacterialmoleculesthatbacteriacreateorviruses.Theydothisinbladdercancerforexample.They'llusethesekindofmoleculesthatactivatestronglyactivatetheimmunesystemtothenrecognizethetumor.We'reveryinterestedintheactualmoleculesthatthetumordisplaysthatallowtheimmunesystemtodistinguishthetumorcellsfromthenormalcells.Weknowalotaboutthisfromimmunology.Weknowinfactthatalloftheproteinsthataremadeinsidethecellandmakethecellworkanddoallitsstuffareessentiallygroundupintopieces.

Someofthosepiecesarerepresentativesetofthosepiecesofproteinareactuallydisplayedonthesurfaceofthecellasiftosaytotherestofthebody,"Thisiswhat'sgoingoninmerightnow.Here'sasamplingofpiecesofmyproteins."Inasense,thecellinyourbodyistellingtherestofyourbody,"Here'swhatI'maboutrightnow."Yourimmunesystemisacclimatedtorecognizethosesignalsandit'sconstantlysurveyingyourcellsandsaying,"Lookslikethisoneisokay.Yeah,thisoneisokay."WhenacancercellcomesalongitgetsDNAmutationsandsomeofthoseDNAmutationsthencausetheproteinstobemutatedandsoyougetlittlesnippetsofmutatedproteinsonthesurfaceofacellandthat'swhattheimmunesystemusestorecognize


10

thatsomethingwonkyisgoingononthatcell.

Avaccineessentiallyfunctionstoalerttheimmunesystemthatthisisthekindofthingyoushouldbelookingforinattackingthecell.Thiswholesystemevolvedovermillionsandmillionsofyearsofevolution.Forexampleifacellgetsinfectedbyavirus,theviruswillmakeitsownviralproteinsandthosewillshowupasforeignproteinsandthenberecognizedbytheimmunesystemandthecellwillknowtoattack.It'saregionalphenomenonsoyouwanttogetahotzonearoundthetumorwheretheimmunesystemishighlyactive.Itturnsoutthatinthelastfewyearswe'velearnedthattumorshavethesetricksforshuttingdowntheimmunesystem.

Everythinginbiologyisaboutbalanceandsoovertheseyearsofevolutionactuallyhumancellshaveevolvedawaytosay,"Hey,I'mintrouble.Hey,I'mreallyintrouble,youshouldattackme.HeyI'monlykindofintrouble,shutdowntheattack."Thatladdermessageisusedbycancer,thecancerwillactuallydistortthisnaturalbiologicalprocessandmakethecancercellssuchthattheyaresaying,"Yeah,I'mkindofintroublebutnotsobadsodon'treallyattackme."Newdrugsthatshutoffthatsignalarethemostexcitingthinginimmunotherapy.Theyaretryingtomakesothecancercan'thidefromtheimmunesystemanymorebutitrequirestwothings.

Itrequirestheinhibitionofthese,"Don'tkillme,I'mreallyokay,"signalsbutitalsorequiresthattherewillbeatleastsomething,somedifferentproteinonthesurfacethatthecancerisdisplayingthattheimmunesystemcanlatchontotodistinguishit.Actually,thatisfrom…ImadethislongstorysowecouldgetbacktowhywecareaboutDNAsequencingcancerbecausewehaveprogramsaboutadozenotherlabsnowhavecomputerprogramswherewecantakeasampleofyourcancertissue,sequenceitinaDNAsequencingmachineandthenusecomputeranalysistoinferwhatkindsofabnormalproteinsareinthecancer.

Whatkindsofpiecesofthemmightbeonthesurfaceandhence,whatthecancercellmightbetellingyourimmunesystem.Wealsolookatwhetherit'ssendingoutthesespecialsignalsabout,"Don'treallyharmme."Ifwecantellwhetheracellisactuallydisplayingthatit'sdifferentandalsomaybeshuttingdowntheimmuneresponsethenweknowthatbyreversingtheshutdownoftheimmuneresponse,theimmunesystemshouldbeabletorecognizeitbecauseitisdisplayingsomethingdifferent.Ifitdoesn'trecognizeit,wecouldactuallyinprinciplecustomizeavaccinebecauseweknowhow,whatkindofdifferentsignalweneedtotraintheimmunesystemtorecognizethatcancer.

It'savery,veryexcitingpotentialcominguphere.We'restillyearsofffromactualroutineuseofvaccinerelatedcancer.Yourcousinwasinavery,veryspecialprogramthat'snotroutineinallhospitals.Thenewdrugs,theso-calledPD1checkpointinhibitordrugs,checkpointblockadedrugswhichshutdownthisPD1signalthatthecancerisusingtohidefromtheimmunesystemarenowinalmostroutineuseformanydifferentcancersinparticular,melanomas.Theywereprovedrecentlyfornon-smallcelllungcancerandsoforth.Wearegettingtothepointwherethisisnotexoticanymorebutbecomingpartofregularclinicalpracticebutbeforethevaccinestuffisregular,it'sgoingtorequiremorework.

Dave: There'sasetofgenesthathavebeenidentifiedthatmakepeoplemorepronetoauto-immuneconditions.TheyareontheHLA-DR.I'moneinfourpeoplewhohasatendencytowardsauto-


11

immunity.I'msensitivetotoxicmoldintheenvironment.Iactuallydidadocumentaryaboutthatbecauseitabsolutelyjustcausesinflammationneurologicallyandthroughoutmyphysiologywhichalsoincreasesmyriskofcancerandall.AtleastaccordingtosomeofthestuffI'vereaditdoes.Now,that'sirritatingbecausemyplanistoliveto180-years-old.

Isaiditwasmyplan.I'mdoingeverythingIcantogetthere.Idon'tknowifIwillornotbutI'msureI'mgoingtodoeverythingpossiblethatnormalpeoplewouldneverthinkabout.HowquicklyamIgoingtobeabletouseCRISPRorsomeothertechnologytojustgointhereandgetridofthosefewannoyinggenesandsomemeaningfulsubstantialsubsetofmycells?OverthecourseofsevenyearsasIreplacemycells,Icanjustbedonewiththat.

David: VeryinterestingthatyoubringuptheHLAgenesbecausetheyarethescaffoldsthatactuallyholdtheproteinstoshowtheimmunesystem.TheHLAgenesareamazinginthesensethattheyaregenericproteinsthatwillloadonasmallpieceofrandomproteinfromsomeproteinthat'sbeingmadeinthecellandthencarryittothesurfaceanddisplayittotheimmunesystem.TheimmunesystemcomesalongandrecognizesitbythesecellscalledTcells.Theyarepartofyourwhitebloodcells.TheTcellshavethesereceptorsandtheyareconstantlylookingtoseewhetherthepeptidethat'sbeingdisplayedbyyourHLAmoleculeisofthenormalkindorwhetherit'ssomethingweirdthattheyhaven'tseenbefore.Thatisthekeyeventinimmunity.It'sthekeyeventindecidingwhetherit'sokayorwhethersomethingiswrong.

Now,ifsomethingiswrong,genuinelywronglikeavirushasinvadedthecellorisacancercellthenyouwanttheTcellstorespond.YouwanttheTcellstogointoemergencymodesendoutthecytokinesignalsandalloftheseothersignalsthatsay,"Somethingiswrong,we'vegottostartkilling."ThisultimatelythekillerssocalledliterallykillerTcellsareverypowerfulintermsofattackingcells.It'saverypowerfulsystembutitalsohastobecarefullycontrolledandsotheautoimmunityproblemsthatyourefertocomeinwhenthere'samis-adjustmentoftheimmunesystemssothatyouhavepropensitynowfortheimmunesystemtomakeamistakeandthinknormalcellsneedtobeattacked.Then,onceyourimmunesystemstartsattackingcertainofyournormalcellsthenyouhaveproblems.Youmayhavearthritisifit'sattackingthecellsinyourjoints.

Dave: IhadarthritiswhenIwas14inmyknees.Idon'thaveitanymorebutIdid.

David: Yup,youmayhavemultiplesclerosisifitattacksthesheetsonyourparticularaxonsandyourneuronsandsoforth.

Dave: I'veneversaidthisontheairbutIamreasonablycertainthatIwouldhaveendedupwithMShadInotradicallychangedmybiologyusingthelifestyleandalltheotherthingsI'vedone.I'veneverbeendiagnosedwithitbutIcouldseewhatwasgoingoninmynervoussystemwithneurologicalinflammation.I'mfriendswithTerryWahls,MindingmymitochondriaandIamstrongernowat43thanIwasat23becauseI'mawareoftheproblemsandabletotakeactiontoturnthatoff.Mostpeoplearen'tbutIsuspectIwouldhavebythetimeI'm50IprobablywouldhavehadMS.Idon'tthinkthere'sachanceinhellthat'sgoingtohappentomenow.

David: Good.That'sthemostimportantthingisthehealththing.IcouldsayactuallyI'mstrongernow


12

at62thanIwasat43.

Dave: Good.Wow.

David: It'spossibletokeepitup.

Dave: That'spowerful.

David: MainlybecauseI'vestartedworkingoutinthelastfiveyears.Yougettoacertainageandyouthink,"OhmyGod,ifIdon'tdosomething,"I'mnotreallypayinganyattentionandnotreallydoinganythingforregularhealth.NowIambutbacktotheimmunesystem,Ithinkit'snotsomuchthatyouwanttoactuallygoinandtrytogeneticallychangeyourHLAmolecules.Imean,everycellinyourbodyhastheaversionofHLAgenesthatyougotfrommomanddadandmysuggestionisthatyougottolivewiththat.It'snotgoingtobeeasytochangeallthosecells,theymakeupyourwholebody.Youdon'twanttostartchangingyourfundamentalgenetics.

Dave: SureIdo,whynot?

David: Okay.Let’snotgothererightnow,youmaywanttodothatbutthat’snotgoingtobetheeasyroute.

Dave: Agreed.Okay,I’mwithyouthere.

David: Whathappensisthenthere’sgottobesomeparticularpeptidesthattheseHLAsareexpressingtoyourimmunesysteminparticularcellsthatwheretheproblemisarising,right?There’ssomeparticularmis-recognitionphenomenonthat’shappening,it’snotalloveryourbody.It’sonlyundercertaincircumstancesthatthesecertainHLAswillproduceaninappropriateimmuneresponsethatcausesautoimmunity.Ifwecouldtargetjustthat,justlikewedocancer,ifwecantargetthatinappropriateimmuneresponsespecificallywithoutmessingwithanyotherpartofyourbodyoryourimmunesystem,thatwouldbeinmymindamoreappropriateapproachtoautoimmunity.

Thebeautifulthingaboutthisisnowwehavebillionsofdollarsbeingpouredintoimmunotherapybecausecancerisahuge,hugetopic.Wearelearningaboutthemoleculardetailsoftheimmuneresponseatanoutstandingratebecauseit’sdrivingbillionsandbillionsandbillionsofdollarsofinvestmentinnewimmunotherapydrugs.Partofthatwe'llhaveandI’llmakeapredictionherethatmightbealittlecomforting,partofthatwillhavethesideeffectofgreaterunderstandingandgreatertechnologythatwillallowustomanipulatetheimmunesystem.Wecanimagineaworldinadecadewherewecanmeasureexactlywhatyourimmunesystemisdoingatanytimeandwecansay,“Okay,thislooksgreat.Allright,youhadacoldtwoweeksagoandyourimmunesystemreactedtoit.

Itlooksit’sappropriatelycalmingdown,right,thensowe’renothavingTcellsthatarereactingtothatrhinovirusanymore,wedon’tneedthem,”andit’sgreat.Whatwewanttobeabletosayisbutifthisisindeedthecasewe'restartingtoseeanautoimmunereactionincertaintissueswhereyouhavetheseparticularTcellswiththisreceptorthat’srecognizingthisdisplayed


13

peptideandthatisaninappropriateinteractionbetweentheTcellandthenormalcell.Weneedtostopthatinteraction.Ontheotherhandyoumayalsohaveatiny,tinycancerthat’sstartingsomewhereinyourbodyandyourimmunesystemisnotrecognizingtheabnormalprotein.

Theseeventsaretwosidesofthesamecoin,intheonecaseyouwanttheTcelltorecognizetheproteinandtheothercaseyouwantedtostoprecognizingorstopreactingtotheprotein.That’stheautoimmunitycase.Becausecancerandautoimmunityaretwosidesofthesamecoin,themoreweunderstandthesystemofhowtheimmunesystemrecognizesthepeptidesthatarebeingdisplayedandthemorewehavetechnologytomanipulateit,thebetterwe’llgetonbothsides.Ithinktheenormousinvestmentisgoingtopayoffwithinadecadewherewe’llbeabletohavemoreprecisemanipulation,moreprecisesurveillanceandthenmoreprecisemanipulationoftheimmunesystemwhichcouldsaveyouawholeworldofpaininthefutureifyouhaveanautoimmunediseaseandit’swellworththeinvestment.Imeaninternationalinvestmentinresearch.

Dave: ItisoneofthemostimportantthingsyoucandobecausethisstuffaffectsatleastoneinfourpeopleandprobablymorethanthatifyoulookatjustsubsetslikeHashimoto'sandthingslikethatthatarealmostrampantatthispoint.Now,I’mdebating,IwanttotalkabouttheGlobalAllianceforGenomicsandHealth,thecomputerhackersideofme.I’mreallyintriguedatsharingthisvolumeofdatasecurely.BeforewegothereI'vesaidIwanttoseeifIcaneitherfreakyououtoroffendyougivenwhatyoujustsaidaboutimmunepresentation.OneofthethingsthatreducedmyautoimmunityandIhaven’ttalkedaboutthisonaireitherbeforebutIjustwanttopickyourbrain.

TellmeifI’mcrazy.Whenyou’rehavingautoimmunereactionyoureleasealotofantigensinyoururineandthere’sdiscussingAyurvedicpracticesofdrinkingurineandthingslikethatthatdon’tworkbutaremeanttoworkviathispathway.However,whenyoutakethoseantigens,collectthemfromurinewhenyou’rehavinganimmunereaction.Thesearetheinappropriateimmunemolecules.Theyareimmunemoleculescreatedbyaninappropriateresponse.Ifyoupresentthemtotheimmunesystemasforeignmoleculesyoucanmakeantibodiestoyourownantibodiesandcancelthemout.

WhenIhaveabigautoimmuneattackIactually,nowthisisgoingtosoundcrazy,Ididn’tinventthis,Iwilltaketheurine,I’llmixitwithLidocaineandI’llinjectitthrougha50microporefilterintomymuscletissue.Itpresentsthoseantigens.IcaneatfoodsIcouldn’teatbeforeandIhavealotlessreactivityeventothethingsI’mmostreactiveto.Itseemstobeworkingandit’slikecompletelycavemanlevelimmunotherapybutI’mkindoflikingmylife.AmInuts?

David: You'renuts.I’lltellyouastory.BeforeIwentbacktograduateschoolIworkataranch.It’sanoldfamilyranch.We’vehaditinnearPasoRobleswehadinthefamilysincemy1920.Mygreatunclestarteditandhegotillanddiedandtherewasnobodyreallytheretotakecareoftheproperty.InbetweenundergraduateschoolandgraduateschoolIspentacoupleofyearsmanagingtheproperty,thefarm,wherewegrewalmondsandwalnutsanddozensofdifferentvarietiesoffruit.It’salittleorganicfarm.


14

Dave: Gorgeous.

David: Ihadahellofatimewithpoisonoak,veryreactivetoitandbeingoutinthefieldIwasalwaysseeming…Itwasseeminganannoyanceandyoucouldn’tgetawayfromit.IwasdowntownonetimewhenPasoRobleswasalittletownandnotthewinemeccathatitistoday.Iwastalkingwithanoldfarmerthere,CharlieYearwoodwashisname.Hedidalotoftractorworkaroundthearea.Ihadnoticedhimonajobburningpoisonoakandthenactuallydrivinghistractorintoittocompactitandbreathingthispoisonoaksmoke.Ijustcouldn’tbelieve.That’stheworstexposurethatyoucanhave.

Dave: Youcoulddiefromthat.

David: Youcoulddiefromthat.Youcoulddefinitelydiefromthat.TheoilsofthepoisonoakcominginandIsaid,“Charlie,howisitthatyou’renotallergictopoisonoak?”andhesaid,“IwaswhenIwasyoung.IhadahorriblereactiontopoisonoakbutIfoundthiswomandowninPasoRobles.Somepeoplecallherawitchbutshesaidallyouhavetodoisgooutthereinthespringtimewhentheleavesarejustaboutthesizeofasquirrel'searandyoujusteatoneofthem.Comebackthenextdayandeatanotheroneofthem,youdothatforsevendays,youneverhaveaproblemwithpoisonoakagain.”

Somewhatthesameprinciple,right,you’rekindofoverloadingyoursystematsomepointandtryingtogetyourimmunesystemtoswitch.Idon’tknow.Iwasstupidenoughatthispoint.TothinkthatthisshouldmightworkandIwaslivingtherewithmybestfriendDonandIwentoutonemorninginthespring,pickedtheleaf,cheweditup.Whatthehell?Herewego,right.Gotbackhome,spentthenightworryingaboutit.Nothinghappened.Gotupinthemorning,toldDonwhatIhaddoneandIsaid,“Lookthisisproof,Ifeelgreat.

Thisisgreat.DayoneI’mtiptop.”Iwentdown,ateanotherleaf.SeconddayIcamebackandsoforth,wenttobed.Iwokeupinthemorningmywholesystemwasswelled,mywholemouthwasswelledup,mywholeinternaldigestivesystemwasonfire,Iwasatotalmess.IgotverylittlesympathyfromDon,theonlythinghesaidasIrecallis,“Iguessyoudon’tknowhowbigasquirrel'searis,doyou?”

Dave: Thiswasallajoketoseeifhecouldgetyoutodoit.

David: Right.Charlie,yeah.Charlie’sgoodjoke.Idon’tknow.Ithinkyou’recrazy.

Dave: IhavebeencalledthatbeforeandImightsustainedoneortwobiohackinginjuries.Iappreciateyoubothsharingthestoryandrenderingyouropinionthere.IfiguredIwasunlikelytodoalotofharmandI’malwayscurious.Ithinkifit’snotgoingtoreally,reallycausepermanentnegativeeffectsinmywork,someone'sgottobetheguineapigitmightaswellbeme.

David: Right.

Dave: Let’stalkaboutsharingthehumangenomebecausenowthatwe’vegotthisdataandthedataisrelativelyaffordable.IjusthadmyentiregenomesequencedatHLI.Ididn’thavetheresults


15

yetbutthefullthingwhichisprettycoolthatameremortalcangetitdone.It'sstillreasonablyexpensive.

David: Priceisstillcomingdown.

Dave: Itis.

David: Mygenomesequencing.

Dave: Howmuchisthecurrentprice?

David: Thecheapestpriceisacoupleofthousandbucksifyoujustgetthemachinetodoitandwithouttheinterpretationandsoforth.That’sgettingtobewithinrangeoflargerandlargernumberofpeopleandthenofcourseifyoujustwanttosnipit.Youwanttolookatthetinyfractionsayoneoutofathousanddifferentpositionsthatarethemostinformativepositionsinyourgenome,youcanjustgoto23andMeand95bucksIthinkyoucangetaglimpseIwouldsay,asnapshotofsomeoftheimportantpartsofyourgenome.Whetheryouwantthewholethingdoneorjustalittlebit,itbeatstheprice,itcanrangefromahundredtoseveralthousanddollarsbutthesearenotundoablenumbers.

Dave: Whatarethebigbarriersofsharingthisdata?Wehaveaworldlet’ssaywherenowthousandsofpeoplehavetheirfullgenomesequencedthensoonhundredsofthousandsormillionsofpeople.WhatarethebarrierstodoingthisandwhatareyoudoingatGlobalAllianceforGenomicsandHealthtosolvethis?

David: Whenwedidthefirstgenomeaspartofthepublichumangenomesequencingprojectwewereveryproudtobeapubliceffortthatwasgoingtoshareallofourdata.ReallythedayJuly7ththatwepostedthat,July7th2000wasthebestdayofmylife,Imeanit’sthedayI’mmostproudof.Wesharedthatfirstglimpseofourgeneticheritagefreeandunrestrictedasopensource,opendataontheweb.Thatwaspartofthewholestructureofthepubliceffortthatitwasscientistallovertheworldjusttryingtohelphumanitymakingthisinformationfullyopenandavailablesothatwecouldmostrapidlyadvanceourmedicalresearchandourbasicbiology.

Let’sfaceittheunderstandingofwhoweare.Evolutionistheprocessthatcreatedourgenomeoverbillionsofyearsfromourdistant,distantancestorsandtheresultsofthatarereallytheproductofuntoldnumbersofstumblesandtriumphsbyourancestorsthroughtheeons.Thisisafundamentalscriptforhumanitythathasbeensculptedbysomuchpainandtriumphthatyouhavetomakeitinouropinionpublicandsomethingthatwecannowcherishandunderstand.Whathappensaswegotnowintomedicalsequencing,clinicalsequencingisthatthetendencyisjusttheopposite,thetendencyistolockdataupimmediatelyandnottoshare.PartofthatisjustHIPAandthewholetraditionofmedicalprivacy.

Dave: HIPA,forpeoplelisteningdefineHIPA?

David: Yeah,thisistheHealthInformationProtectionActthatmakesurethatwhensomebodyasksaboutyourmedicalinformationtheydon’ttellthatpersonunlessit’syouoradesignated


16

relativesothatpeoplecannotgospyingorsnoopingaroundonyourhospitalrecords.Now,thereareverygoodreasonswhywedon’twanttoletarbitrarypeoplehaveaccesstoourmedicalrecordsandtheDNAisincreasinglypartofthemedicalrecords.We’renotarguingthattheDNAandalloftherestofthemedicalrecordshouldjustbenamedpublic.Theproblemisthatwhenyoustarttonotevenmakethisinformationavailableforresearchthenyou’relosinganenormousopportunityandcancerisagreatexample.

Weknowthattherehavebeenmutationsincancertumorsfromtheverybeginningandweknowthatthereareuntoldmillionsofdifferentcombinationsofmutationsinthosetumors.Wewillnotbeabletofigureouttheimportantonesthatweneedtodeveloptherapiesforversustheunimportantonessometimescalledpassengermutationsthatdon’tdoanything.Unlesswehavealargenumberofcasestostudy.Ioftensaythatifyoujusthaveonegenomeyoucan’tlearnanything.It’sonlybycomparinggenomestoeachotherthatthepatternsemerge.Anybodywhoknowsstatisticsalsocanunderstandthatthere’sasignaltonoiseratioproblemwhenyouhaveonlyverylittledataandalotofvariables,alotofthingstolookat.

Thegenomeisaclassicexampleofthat,there’sthreebillionbasesthatcanchange.Therearealotofvariablestodealwithandinordertodothatweneedtolookatalotofgenomes.ThefocusoftheGlobalAllianceforGenomicsandHealthwhichIco-foundedthreeyearsagoistocreateamechanismsotheworldcansharethesegenomicdata.Therearecertaintypesofgenomicdatathatcanbesharedopenlyandpublicly.Forexampleit’sreasonablethatevenifyoudon’tshareyourgenomethatyougotfrommomanddad,yoursocalledgermlinegenometechnically.Youmaystillwanttosharethechangesthathappenedinyourcancertumorbecauseyou’renotgoingtopassthoseontoyourkids,theyarenotprivatetoyou,theyarelikeanyothermedicalsymptom.

Weneedtoaccountforthefrequencyofallofthesemedicalsymptomsincludingthegeneticvarianceaswellastheothermeasuredvariance.Wehaveaprogramrightnowthatwe’retryingtopushcalledtheCancerGeneTrustwherewe’retryingtogetpeopletosharethegeneticvariancethatoccuronlyintheircancerandjustpublishthemopenlysoeverybodycanresearchthose.Ifwedothisrightthere’snoprivacyproblemthere,theproblemisthatthegeneralpublicdoesn’tunderstandthedistinction.It’sascientificdistinction,right,betweenDNAthat’schangedinthetumorversusDNAthat’spartofyourcellsthatyou’regoingtopassontoyourkids.Thatgetscomplicatedtoexplainthatbutifwecangetthatkindofthingtobesharedthatwouldbegreat.

Now,therearealsoarecasesthoughwherewewanttoshareinformationfromyourgermlineDNA,informationthatyouwillpassontoyourkids.AnotherprojectwehaveisatheBRCAchallenge.YoumayknowthegeneBRCA.ManypeopleknowitbecauseAngelinaJoliemadethefamousannouncementthatbecauseshehadageneticvariantinherBRCAgenethatmadeherhighlypronetobreastcancershewasgoingtohaveadoubleradicalmastectomy.Thatcertainlywasawakeupcallallovertheworldtobetheimportanceofthisparticulargeneandtheimportanceofgenetictestingwhenitcomestothinkingaboutandplanningforyourfuture.

TheproblemisthatrightnowwhenwomengointogettestedforBRCA,averysignificantpercentageofthosewomenaretold,“Yes,youhaveanunusualvariantinthegeneBRCAbutit’s


17

avariantofuncertainsignificance.Goawayandworryaboutitbutwecan’ttellyouanythingaboutit.”Whatahorrible,whatahorriblereportforawomantogetandthere’soneandonlyonereasonforthatisthatwehaven’tsharedthedata,wehaven’taccumulatedenoughobservationsofthatvarianttobeabletodecidewhetheritisassociatedwithbreastcancerornot.Ifweonlybeensharingthedataweprobablycouldbeabletotell.TheBRCAexchangeisaboutgettingtheworldtosharethatdata.

Now,inthiscasewe’resharingitwithexperts,we’renotpublishingitopenlyontheweb.We’renotaskingwomentopublishtheirBRCA,fullBRCAgenesequencethatthesameonetheywillpassontotheirkids.We‘renotaskingthemtopublishthis,we’reaskingthemtoshareitwiththeexpertsandlettheexpertshelpclassifythevariantssothateveryonegetsabetterdiagnosis.Thosearetwoprojects,onewhereyou’republiclyopen,onethatwe’retryingtoatleastsharethegenomicinformationwiththeexperts.

Dave: In2011atthebigdataconferencecalledtheGigaomConferenceinNewYorkIproposedasystemliketheonethatyou’retalkingabout,apolicybasistoexposesomeofyourgeneticorlifestyleinformationforinstanceyourfitnesstrackerinformationsothatyoucouldshareitwithyourcommunity,youcansharewithyourdoctor,yousellittoadrugcompany,youcansellitwithoutyournameonit,youcouldassociatedifferentthings,doitallbypolicy.Essentiallycreateamarketplaceforyourdatabecausealotofpeoplealsoreact,“Idon’twantbigpharmadoingresearchonmygenes.”BasicallymostpeoplethatIknownowkindoflookatbigpharmaasnotnecessarilyhonestlikeonestepawayfrombigtobaccoandfranklyifthey’regoingtopatentoneofmygenesIgetacutoryouguysdon’tgetmygenes.

David: Thatattitudehasgottochange.ThesolutiontothatistopreventpatentingandthisisveryrelevantinthebreastcancerareabecausetherewasonecompanyMyriadGeneticsthathadtheexclusivepatentonBRCAgenetestingandthatwasthrownoutbytheSupremeCourttwoyearsago.

Dave: Whatawin.

David: Hallelujah.There’sastepforward.Ithinkthegoalisnottokeepinformationfromthepharmaceuticalindustrybuttomakesurethatthey’renotmisusingitinthesenseofexclusivelypatentinggenesbecausewedoneedpeopletodevelopdrugs.You’rereallygoingtocutyourselfshortifyoucompletelycripplethepharmaceuticalindustry.Iintendtotakealessradicalviewofthatbutgoahead.

Dave: I’mspeakingforalotofpeoplelisteningtotheshowandIhavenofundamentalproblemwithdrugs.Drugswhosavelotsofpeople’slivesprobablyincludingminewhenIhadareallybadinfectionorsomething.

David: That’sright.

Dave: Noproblemthere.Someofthebusinessmodelsandbehaviorsassociatedwiththesecompaniesareethicallychallenged.Forinstancewemakedrugsthatreversetheeffectsofthepesticidesthatwesellfromtheotherarmofthecompany.Thatkindofcraphastostop,MonsantoI’m


18

talkingtoyou,allright.There’sotherdisturbingthingslikethatthatIthinkpeoplehavewokenuptoandthey’renotwillingtocontributetothatsystem.Ifyouputtheminahospitalandsay,“There’satumorthisbiginsideyourhead,”they’regoingtogladlyconsumewhatevercocktailofthingsisgoingtogetridofthat.Assumingthatitisacocktailofdrugsthataregoingtodoit.Wehaven’ttalkedaboutvitaminDincancer,wehaven’ttalkedaboutketosisandcancer,someoftheotherthingsthatweprobablywon'tgettointhetimewegot.

David: YouhavetotalktomybrotheraboutvitaminD,MarkHaussler.HeisoneofthemajordiscoverersofthehormonalformofvitaminDandreally,reallyisanexpertonhowitincreaseslongevityandmayhelpwithcancerandsoforth.He’sdevotedhislifetothestudyofvitaminD,brilliant.

Dave: What’shisname?

David: MarkHaussler,mybrother,myolderbrother.

Dave: Wouldyoufacilitateanintroduction?

David: Sure,I’llhavehimon.Yeah,he’sgreat.

Dave: Iwouldloveto.I’vebeenusingvitaminDandlookingatthatinthevariousinteractionswithlightforalongtime.Thatwouldbefantastic.Whataneatfamily.Itmustbeamazing.Let’stalkaboutwhatyou’redoingwiththeblockchainwhichforpeoplelisteningthisiswhatBitcoinusesandthisistheideathatyoucantakedatathatyouwantcontroloverwhoseesitandwhodoeswhatwithit.Youcanencryptthedatawiththedatathatcamebefore,thedatathatcameaftersoyoucansortoftrackwhetheranyonehasaccesseditorifanyonehasmessedwithit.Doyouhavethisrolledoutforgeneticdata?CouldIsharemystufftodayonblockchain?

David: Wedon’thavethisrolledout.We’rejustworkingwiththesystem,forthecancergenetrustwehaveoneversionthatusesblockchainandoneversionthatdoesn’tuseblockchainthat’sevensimplerbutjustasastart.Whatwewanttodoismakesurethatwegetpeoplestartingtosharerightawaywithalittleoverheadandjustgetitgoingandthenaddmorebellsandwhistlesaswegoon.Theblockchainwouldbeimportantfortransparency,we’reusingitasapublicledgerwhichyoucanrecordallofthetransactionsthathavetakenplace.SimplesttransactionisSuedecidedtosharethisgeneticinformationandBillyusedthatgeneticinformationandthenBobsharedthisinformationandsoforth.

Allofthesethingsbeingtransparentandbeingavailableinapublicrecordthatcan’tforgedorcheatedorsomethinglikethatisvery,veryimportant.Insensewhenyousaysharethedatathisistheotherpartofthis,mostpeoplearethinkingsharethedatawithwhoandwhohascontrolofthedata.Whattosharethedata?WegiveitalltoGoogleandtheydistributeitorwegiveitalltotheUSgovernmenttheybuildabigdatabasethattheworldcanuseandsoforth?Mostpeopleareunhappywiththosesolutions,theyreallywantsomethingthat’sorganicliketheinternetitselfsothatweareessentiallypostingthatdataontoashareddatabasethatisessentiallyagloballyshareddatabase.


19

Inthattheblockchainmaybeonemechanismforkeepingtrackofwhodoeswhatintermsofsubmittingdataandusingthedata.Ifit’stransactionalthenyoucanactuallyusethattocreateaneconomyofthetypeyouaretalkingabout,right.Youcankeeptrackofwho’susingyourdata,youcangetvarioustypesoffeedbackorevenvaluebackfromthedata.I'mhighlydiscouragingoftheideaofsellingyourgenomicdataatthispoint,Ithinkthatwillholdresearchback.

Dave: Agree.

David: Iwouldlikepeopletofirstconsidercontributingdatatoscienceforthepurposesofknowingthatyoudidsomethinggoodfortheworld.

Dave: Ifullyagree.Isupportthat.

David: WerunapediatriccancerprogramandI’lltellyoubrieflyaboutit.TheGovernorofCaliforniaannouncedtheprecisionmedicineinitiative.InCaliforniatherewasaseriouscompetitionforthataboutayearagoandofalltheapplicationswewerethrilledthatourswasoneoftwothatwerepicked.TheprogramiscalledTheCaliforniaKidsCancerComparison,itisideaofintroducingDNAcomparisonintothetreatmentofkidswithcancer.Akidcomesintooneofthehospitalsthattreatskidswithcancerandthey’reonlyaboutadozeninCalifornia,lessthanadozeninCalifornia.Theywouldbereferredfromasmallerclinicupintooneoftheselargerhospitals.

Eventhecaseasthekindthatthereisastandardtherapythat’sverylikelytowork,inwhichcasethekidgetsthistherapyorthechildhasatypeofcancerthatwereallydon’tknowhowtotreatorthechild,theworstcaseisthechildiscomingbackwitharecurrentcancerthatwastreatedbeforeandnowhasemergedresistanceorisre-surgingagain.Thoseareparticularlyhardtotreat.TheproposaltothegovernorandthestateofCaliforniaiseverykideitherthelattertothecategoriesiftheircancerishardtotreatfromthegetgoorthey’recomingbackwithasecondcancer.Theyshouldhavetheirgenomesequenced.

Weshouldlookatallthemutationsinthetumorandtrytocomeupwithaprecisionmedicinetreatmentforthischild.Thiswasaccepted,wearewellintoit,wehavethreeclinicaltrialswhichisamechanismfortryingtodocreative,morecreativethingswithtreatment.OneisinthePediatricCancerGroupatStanfordwithAlejandroSweet-Cordero,fabulouspediatricianwhoworksintheareaofpediatriccancer.He’snowinvitedustoparticipateintheweeklytumorboardsthattheyhavewherewediscusstheindividualhardtotreatcases.WepresentallofourgeneticanalysisalongwithregularcanceranalysisandallofthebestmindsatStanfordthinkabout,“Okay,whatcanwedoforthiskidwho’sfailedtheoriginaltherapyandnowwe’relookingforanalternative?”

Thisisjustanenormousopportunitytohaveanimpactatthisstage.Whatwe’remainlysufferingfromintothisandasimilarprogramatUCSFandasimilarprogramatUCIrvine,Children’sHospitalofOrangeCounty.We’reallinvolvedinthesethingsandwe’refindingthatthebiggestfrustrationisthatthesekidshavedifferentcombinationsofmutationsandthereisn’tadatabaseouttherethatwecanlookuptofindsimilarkids.I’mgettingbacktothis,thisis


20

whytheGlobalAllianceissoimportantthatyouknowthereareotherkidsthathavehadmutationslikethis.

Goddamnitwhycan’twefindthemandunderstandwhathappentothemandallowittotreatthenextkid.Ifwetalktoparentsdotheywanttosharethisinformation,yestheywanttosharethisinformationandpurelyforthesatisfactionofknowingthattheirchild’sstrugglehelpssomeotherchild.

Dave: Absolutely.

David: That’senough.Theydon'twanttogetpaid.

Dave: Notatall.

David: Theydon’tcarewhetherapharmaceuticalcompanyisgoingtomakeadrugoutofit.Theywouldliketojusthelpotherkidsandtheywanttosharethisinformation.Wearetryingtohelpthemsharethisinformationsoeverykidhasafightingchance,everykidcanlearnfromeveryotherkidwho’severhadcancer.ObviouslyIgetalittleagitatedaboutthisbutthat’sreallyimportant.

Dave: That’swhatthisisaboutishelpingpeople.AfriendofmineAlexanderCarmichaelstartedacompanycalledPatientsLikeMe.

David: Yes,Ithinkit’sgreat.

Dave: Okay,andIloveAlexander,she’suniqueandshehasautoimmunity,right.InfactIwouldarguesheprobablyhadmoldexposuregivenallofhersymptomsbutsheandIhavetalkedaboutallkindsofstuffandIhavenoideaifmoldisitornot.She’sbeenveryopenaboutthis,Iwouldn'ttalkaboutit.Anyway,shesaid,“Okay,there’stensofthousandsofpeoplewhodealwithallthesestuffeveryday,whydon’twegettogetherandrunourowntrialsbecausethingsaretooslow.”Theydidexactlythesamethingbuttheydidn’thavethegeneticdatabecausethiswasfiveyearsago.

David: Exactly.

Dave: Whatwe’retalkingaboutnowispatientslike2.0withgeneticdataandyou’reputtingthestructuresinplaceinaprofittofacilitate,actuallycontrolforparentswhohavesickkids.Findtheotherthreesickkidslikethis,findthegenometherapythatworkforoneofthemandmaybeit’llhelpme.Weowethattoeachotherashumanbeings,Isupportthatalltheway.

David: Ilovethatline.Canweusethatline?

Dave: It’syourstodoit.

David: “Weowethistoeachotherashumanbeings,”that’sexactlywhyweneedtosharethisdata.


21

Dave: That’sthemotivatingfactorforwhyIshareallthebiohacksIdotoo.NoonegavemeaninstructionmanualandIweighed300poundsandIhadarthritisandalltheseotherthings.I’mirritatedthatIspent20yearsandalmostamilliondollarshackingitbutheyI’mhappyI’mhere.It’sbeenafascinatinginterviewandI’vegotonequestionforyou,David.

David: Okay.

Dave: Ifsomeonecametoyoutomorrowandtheysaid,“Basedoneverythingyou’velearnedinyourlifenotjustinyouracademicsbutineverything,Iwantthreepiecesofadvice.IwanttoperformbetterateverythinglikeIwanttokickassateverythingIdo.WhatarethethreemostimportantthingsIneedtoknow?"

David: Thisgoesbacktotheclassickindofresponsetothegenomeskeptics,right.Theclassicstoryisyougetyourgenomesequencedandyougetthetotalquantifiedselfandyouknoweverythingaboutitandyouaskthebiggestguruintheworldandhesays,“Yeah,there’sthreethingsyouneedtodo.Exercise,eatrightandgetplentyofsleep,”“Thankyou.Ipay$30,000.”

Dave: Thosecomeupremarkablyoftenasanswerstothatquestion.

David: Yeah,andthisparableisactuallyhadsomeessencetoitthat’simportanttounderstandisthatthehumanbodyandorphysiologyandourhealthisavery,verycomplexprocess.Weareonlygraduallystartingtounderstanditandpartofitisbecausewewereworkingwithitasablackboxforsolong.Thatthosethepreviousmedicinejustsimplywasinthishopelessstate,I’mnotbeingabletoopentheboxandseewhat’sgoingonandwe’reonlynowstartingtomakethattransitiontowherewecanstarttounderstandthecomplexityofwhat’sgoingon.

Inthereit’sstillincrediblydauntingandthere’sstilllotsofthingswecan’tmeasureandtherearealotsofmodalitiesthatwecan’tmodel.Untilwegetalotmoredataandalotsmarter,it’sstillgoingtobedifficulttogiveaverypreciseplanformaximumhealth.AllIcansayistheonlywaywe’llgetthereismassivesharingofdata,massivedataofanalysisandengagementofeverybody.Iwelcomecitizenscientistforgettinginvolvedandthey'vebeenshutoutcompletelyupuntilnow.Therewasnowaytheycangetaccesstoanydatathattheyneeded.Weneedtobringthebestmindstobearonthis.

Dave: SomeofthosebestmindsareprobablybiohackerswhoaredealingwiththeseconditionsandareunwillingtokeepdealingwithitandI’moneofthem.

David: Yeah,that’sgreat.Youhavethestrongmotivationandbrillianceandsoweneedtomakeanavenuethroughaglobalsharingandinternetbasedinfrastructurewherewecansharethesedata.Stillprotecttheprivacyoftheindividualsinformationbutneverthelesssharewithindividualswhocanhelp.

Dave: David,wherecanpeoplefindoutmoreabouttheinitiativesthatyou’reworkingandhowcantheysupportthem?

David: GotoGlobalAllianceandHealth,globalallianceforgenomicsandhealth.org,youcanga4gh.orgis


22

thekindofthegeeksite.IfyoujustGoogleGlobalAllianceforGenomicsandHealth,justGooglethatphraseyouwillgetthemainwebpages.It’sallaboutourprojectsandourleadership.Wehaveanenormousparticipationmorethan400differentinstitutesfrom40differentcountriesaremembersandareparticipating.Ourscientificadvisoryboardisveryillustrious,FrancisCollinsthedirectoroftheNIHhereforexampleisonourscientificadvisoryboard,justtodroponenamethere.Wedohaveasubstantialinvestmentindatasharingatthispointandifyou’reageekyoucangodirectlytothegithubsitewhereyoucanseeallofouropensourcecode.

Anyonecanparticipate,it’saclassicopensourceculture,ifyoustartactuallymakingcreativeenhancementstothecodeallyoudois…Youcancomeoutofanywhere.Wedon’trequiremembershiporanythinglikethatbutifyourcodechangeorpullrequestastheysaygetsthumbsupfromthreedifferentotherexistingengineersontheprojectthenitwillbeincorporatedintothecodebaseandyou’venowbecomeadeveloperfortheGlobalAlliance.ThisistheApachevotingrulesofopensource,right,threeplusonesandnominusonesandyourpullrequestisaccepted.It’sanopenembracing,welcomingcommunityofgeeksthataretryingtomakeadifferenceandwewanteverybodytojoin.

Dave: David,thankyousomuchforbeingonBulletproofRadiotoday.It’sbeenaveryilluminating.Iappreciateyoutakingareallycomplextopicandmakingitsomethingthatallofuscanunderstand.

David: Thankyou.Allright,allthebestwithyourhealthquest.We’llcelebratewhenyou’re180andI’m200.

Dave: It’sadeal.

David: Okay,thanks.

Dave: Thanksforwatching.Don’tmissout.Tokeepgettinggreatvideoslikethistohelpyoukickmoreassatlife,subscribetotheBulletproofYouTubechannelatbulletproofexec.com/youtubeandstayBulletproof.

transcript – saying genome to cancer with david … · transcript – saying genome to cancer...

Documents