new technologies and human enhancement

8/13/2019 New Technologies and Human Enhancement

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New Technologies and

Human Enhancement

prof. J. SavulescuUniversity of Oxford, Uehiro

Centre for Practical Ethics


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Human Enhancement and

Biological Liberation

From Supermouse to

Superhuman

Program on the Ethics of the New Biosciences, Suite 8, Littlegate House, St Ebbes Street,

Oxford

Julian Savulescu, Director


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Scientists at Case Western Reserve University created agenetically engineered mouse runs for up to six hours at a speed of 20 metres per minute

before needing a rest changes to the metabolism of glucose in the blood.

glucose metabolising gene - PEPCK-C is over-expressed in theskeletal muscle-

Metabolically similar to Lance Armstrong biking up thePyrenees; they utilize mainly fatty acids for energy and producevery little lactic acid'.

Purpose:

to study the effects of diet and exercise on longevity and cancerrisk and better understand the genetic basis of inheritedconditions which lead to muscle wasting in humans

Supermouse


Oxford



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More Active: 7 times more cage activity than normal mice

Greater Endurance: Ran 6km on a treadmill (Normal mouse0.2)

Improved metabolism: ate 60% more but had half the bodyweight and only 10% of the body fat of a normal mouse

Extended lifespan: survived longer and looked healthier

Extended youthfulness: mice of 30 months still twice as fastas 6 month old normal mice and reproductively active at 21months (and up to 30 months)

Healthier: Lower Cholesterol levels

Supermouse: The Improvements


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Table 1. Top 10 genetic enhancements

The Doogie MouseBetter memory through overexpression of the receptor subunit NR2B

Color Vision MiceAdding human photopigment allows (at least females) to see new colors.

Methuselah MiceBy reducing growth hormone levels long-lived dwarf mice can be produced. The current recordholder survived 4 years 11 months and 3 weeks, while normal mice have a two year lifespan.

Monogamous VolesNormally polygamous voles can be turned monogamous (and more social) by changing thevassopressin V1a receptor.

Regenerating MRL MiceThese mice regenerate holes punched in their ears as well as some injuries to heartmuscle. (accidental breeding rather than genetic engineering).

Schwarzenegger Mice and Belgian Blue Cows Increased muscle mass through myostatin knockout. Occursnaturally in cows and humans.

Hard Working Monkeys Monkeys tend to slack off until they get close to a reward they have to work for. Ifinjected with a DNA construct that blocks the D2 receptor they work at an even rate.

Anticancer Mice Immune systems that kill cancer cells efficiently and can even help other mice through bloodtransfusions.

Antiobesi ty Mice Protected from obesity and diabetes by their lack the enzyme DGAT1. Their fat tissue can evenreduce obesity and glucose buildup in other mice if transplanted.

Marathon Mice: Overexpress PPAR in their muscles- turn into slow twitch fibers that work well for long-distancerunning. More endurance and increased resistance to obesity.


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Biological Liberation

biological liberation being liberated from the biological constraints

evolution placed on us.

the reason there are no supermen, like the reason

there are no naturally occurring supermice is that itwould have been evolutionarily disadvantageous,given previous environments, to require the vastamounts of food resources to produce this

advantage in speed, endurance and reproduction


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Biological Liberation Our biochemistry is set to Pleistocene

conditions But today, we have a superabundance of

food in the West

We could easily provide the calories to run at thisspeed.

Whereas evolution may have had good reason

not to produce supermen, we could.


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Biological Liberation our lives when we reproduce, whether we get cancer

or heart disease, how long we live, how we performmentally and physically are determined in large partby very basic biochemical cycles in our bodies.

differences between us are often the function of very

small differences in biology. we can now change these basic cycles with radical

results. possibility of humans being twice as fast, living twice as long,

reproducing at 80, not aging, being mentally and physicallymuch quicker is not science fiction.


Oxford



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Julian Savulescu

www.practicalethics.ox.ac.uk

Oxford Uehiro Centre for Practical Ethics

RadicalAlterationofHumans

CurrentPossibilities

Transgenesis

Chimeras

HumanAnimal


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Transgenesis

Currentuses

Medicalresearchchromosome21inmice

Diseaseresistantspecies

Productsusefultohumansbloodclottingfactors,artificialfibres

Xenotransplantation


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TheRealWorldContext:UKResearch

LastNovembertwouniversities,KingsCollegeLondonandNewcastleUniversity,appliedtotheHumanFertilisationandEmbryologyAuthority(HFEA)totocreateearlystage chimeric embryosthatwouldbe99.9

percenthumanand0.1percentanimalinordertoproduceembryonicstemcells (Telegraph).

Scientistsproposedusingrabbiteggs.


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NewsReaction

DocstocreateMootant cells saidTheSun. Scientiststomixcellsofhumansandcows theDailyTelegraphheadlineditsreport.

Theaccompanyingarticletoldreadersthathumancellswillbefusedwithrabbit,cowandgoateggs

opponentsoftheresearch calledtheplans abhorrent yesterdayandclaimedthat

scientistswereundermining thewholedistinctionbetweenanimalsandhumans. Manynewspapers,includingtheDailyMail,publisheddrawingsofachimera (the

wordusedtodescribehumananimalembryos) afirebreathingbeastwithalionshead,agoatsmiddle,adragonsrearandaserpentstail.

thenextgenetichorrorstory beingnightmarishparthumanpartanimalhybrids


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Ethics

thisresearchwouldgenerate EScelllineswithgeneticmutationsthatcausehumandisease

providesamodelforstudyingthediseaseincellculture.

ParkinsonsandAlzheimersDiseases.


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Whycreatehybridembryos?

Thereisashortageofhumanembryos(andespeciallyhumaneggs)forresearch.

Thosecurrentlyavailablearesurplusfromhumanassistedreproductiontechniques(invitrofertilizationor

prenatalgeneticdiagnosis) veryrare

oftenpoorquality

donotcontainallthegeneticmutationsthatneedtobestudied.


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Significance

Creatinghumananimalhybridsassourceofdiseasespecificstemcellshasenormoussignificancefortworeasons


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1.SelfTransplantation

Usingthiskindoftechnology,onedaywemaybeabletotakeaskincellfromapatientwithleukaemia,cloneit,deriveembryonicstem(ES)cells,producebloodstemcells,andtransferthebloodcellsbackasatransplant

afterchemotherapy Althoughhumaneggswouldbeamoresuitablesource

ofeggsfortheprocedure,thetechniquescouldbedevelopedonhybrids


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SelfTransplantation

therewouldbenoneedfordrugstopreventrejection,whichcanbelethal

couldproducetissuetorepairdamagedorgansliketheheartandbrainwithnocapacityforregeneration,

providingradicalnewtreatmentsforstrokeandheartattack,Parkinsonsdisease,andmanyotherdiseases.

RegenerativeMedicine

holygrail ofmedicine.


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2.CellularModelsofHumanDisease

hybridembryoscouldbeusedtostudyinaradicallynewwayanydiseaseinaculturedish

Cloningasingleskincellfromapatientwithadiseasecouldbeusedtoproduceinexhaustibleamountsofcellsandtissuewiththatdisease

experimentedupontounderstandwhydiseaseoccurs.

understandthegeneticcontributiontodisease

totestvastarraysofnewdrugswhichcouldnotbetestedinhumanpeople.

reducetheneedforanimalexperimentationbecause

humancellsandtissues,notpeopleoranimals,couldbeusedtotestnewdrugs.


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EthicsandSinsofOmission FailingtoDoGoodResearch

Tofailtodobeneficialresearchisaswrongasdoingharmfulresearch.

Tofailtoreleaseadrugthatwillsave100,000livesismorallyequivalenttokilling100,000people,andtofailtodevelopadrugthatwillsave100,000livesisthesameasfailingtoreleaseit.

Wemaynotbeabletopointtothosepeoplewhoseliveswouldhavebeensaved,buttheirlivesarenolessvaluable.

Throughafailureofmoralimaginationwemaycontinuetoholdbackcloningresearchandberesponsibleforthedeathsofmanypeoplewhoperishedwhilewedelayedthedevelopmentof

treatments.


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FourObjectionstoESresearch

1.LARGENUMBERSOFEGGS researchrequireslargenumbersofeggsthatmustberemovedfromhealthyyoungwomenatsomeriskoflifeandhealthtothem.

2.ELITISTresearchissaidtobeaWesternluxurywhichwillbeexoticandexpensive,onlybenefitingtherichestcountries.

3.ADULTSTEMCELLRESEARCHshowsgreatpotentialandispreferable.

4.recentresearchshowstheremaybeINFECTIOUSandotherrisks,suchasoccurredwithbovinespongiformencephalitis,oftransplantingtissuebacktopeoplewhenitisgrownonforeign

culture

material

or

uses

animal

eggs


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Response:HybridResearchIsImmunetoTheseObjections

1.wouldrequirenohumaneggstoproducevastamountsoftissueforthestudyofdisease.

2.mayresultinthedevelopmentofdrugsforcommonconditionswhichafflictpeopleallaroundtheworld,

including

the

developing

world.

3notpossibletouseadultstemcellsinthisway.

4.noriskofinfectionfromdrugsdevelopedbystudyingtissueinthisway,asthedrugmoleculeswould

beproducedpharmaceutically.


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Philosophy

ImportanceofConceptualDistinctions(Philosophy)

Theseobjectionsapply(iftheyapplyatall)onlytocloningforselftransplantation.

Theydonotapplytocloningfordeveloping

cellularmodels

of

disease

whichwillhelpus

understandandtreatdisease.


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ThreeOtherObjectionstoHybridCloningresearch

1.CreatesandDestroysEmbryos Response:distinguishbetweenthemoralstatusofwanted

andunwantedembryos. Embryoshaveaspecialmoralstatus potential when

theyareapartofaprojecttohaveachild

Murder

if

kill

a

wanted

unborn

child Negligenceisdestroywantedfrozenembryos Whentheyarenot,theyhaveamuchlowerstatus:

forthatreasonwepermitpeopletodiscardembryosinIVFwhentheyhavecompletedtheirfamily,haveabortion,orusetheIUD.

Thisresearchwouldnotpreventanychildcominginto

existence

who

would

have

existed

if

the

research

had

not

beendone.


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ThreeOtherObjections

2.ChimerasareUnnaturalandCrossSpeciesBoundaries

Thesecondobjectionisthatweshouldnotcreatenewhumannonhumanhybridsorchimerasbecausetheyare

unnaturalandcrosssomekindofprofoundethicalline.


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Unnatural

Response:

scientistshaveforovertwentyyearsbeeninsertinghumangenesintoanimalstocreateanimalmodelsofthehumandisease.

asignificantproportionoftheNIHbudgetgoestothisresearch.

scientistshaveintroducedhumanEScellsintoanimalstostudydevelopmentanddisease


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LessonsFromHistory

Foroveradecadewehavehadthepowertocreatehumannonhumanchimerasbyfusingembryos.Indeed,wehavealreadycreatednewanimalssuchasthegeep,broughtintobeingbyfusingagoatandsheepembryo.

Novellifeformshavebeencreatedandcouldbecreated.

Thisresearchwillbecloselyregulatedandtheembryosdestroyed,so theircreationislesscontroversialthanconventionalresearch


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ThreeOtherObjections

3.SlipperySlopeI:

researchbringsusonestepcloser toreproductivecloning

cloningtoproducelivebornbabies.


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Response:

Reproductivecloningisunlikelytobesafebasedontheobservationthatclonedanimals(mostlymiceandcows)havehundredsofgenesthatareabnormallyexpressed,inparticulargenes

importantfor

fetal

development.

Theresultinganimalshaveabnormalitiesduringdevelopment(whichiswhy95%ormoreofclonedembryosabort),atbirth(largeoffspringsyndrome),orlaterinlife(evenseeminglynormal

mice

often

develop

obesity,

die

prematurely,

or

developmoretumorsthancontrols).


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Response

Theresponsetofearsaboutreproductivecloningisnottobancloning.

Itistobanreproductivecloning.

TheU.K.hasalreadybannedreproductive

cloning,andanyscientistintheU.K.wholetsahybriddeveloplongerthan14dayswouldfacecriminalcharges.

Tobanthisresearchbecauseoffearsaboutreproductivecloningorcreationofhumannonhumanchimerasisnot

justtothrowthebabyoutwiththebathwater.Itispossiblytothrowmillionsofbabiesout.


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Regulation

Thereisnotaslipperyslopebutasetofsteps.

LegislationincountriesliketheUnitedKingdomiscapableofeffectivelyregulatingsuchcontroversialresearch.

Cloning,Transgenesis and

chimeras

illustrate

that

the

claim

that

ifscientistscan,theywillisfalse. Transgenesis andchimerasareempiricalevidencethat

thereisnotaslipperyslopetoradicalalterationofthehumankind.

AsdebateoccurringintheUKnowillustrates,proper

regulationis

what

is

necessary

to

convert

the

slope

to

aset

ofsteps.


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WhatHappenedintheUK?

On2April2008,thefirsthumananimalembryo wascreatedbyscientistsatNewcastleUniversityunderalicencefromtheHumanFertilisationandEmbryologyAuthority(HFEA).

ThelegalityofsuchlicenceshasbeenconfirmedbytheHumanFertilisationandEmbryologyBill(theBill),recentlypassedbytheUKParliament.

TheBill specificallypermitsthe HFEAtolicensethecreationforresearchofseveraltypesofembryosthat

combinehuman

and

animal

genetic

material

(called,

in

theBill,humanadmixedembryos).


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HFEABill

UndertheBill,humanadmixedembryosaredefinedtoincludeembryosthatarealmostallhuman(cybrids)andalsoembryosthatareuptohalfhumanandhalfnonhumananimal(animal):section4A(5).

Humanadmixedembryos:1. Cybrids (orcytoplasmic hybrids):formedbyincubating human

geneticmaterialincytoplasmfromananimal.2. Hybridembryos:formedfromahumaneggandanimalspermor

viceversa;orfromananimalpronucleusandahumanpronucleus.

3. Transgenicembryos:formedbyintroducinganimalDNAintooneormorecellsofahumanembryo.

4. Chimeras:formedbyaddingoneormoreanimalcellstoahumanembryo.


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Differencesbetweenadmixedembryos

Cybrids:99.9%humanDNAmatchedtothepersonfromwhomtheywerecloned;verysmallamountofmitochondrialDNAfromtheanimalscytoplasm.

Hybridembryos:humanandanimalchromosomesbecauseformedbyfertilisingeggandspermfromdifferentspecies.

Transgenicembryos: variableamountofanimalDNAdependingonhowmanygenesaretransferred.

Chimeras:humanandanimalcellsbecauseformedbymerginghumanandanimalembryos.


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SlipperySlopeandPrecautionaryPrinciple

DailyTelegraph hostedadebateprovocativelytitledHasembryoresearchgonetoofar andpublisheda

comment

piece

by

Simon

Hefferwho

wrotethattheprospect[ofsuchresearch]horrifiesme.Itisaviolationandmongrelisationofourspecies,Heffer said,andoneday,somebody

willgrow

abeast

that

has

horns

and

a

tail.


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TheSlipperySlopeObjection

Response

Howvalidistheprediction?

Howbadisthebottomoftheslope?

Woulditalwaysbewrongtoradicallybiologicallymodifyhumanbeings?

O f d U hi C t f P ti l Ethi


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TheThreattoHumanity

Objection

Threattohumanity

Unnatural

Affronttohumandignity

transgressionoftheunspeakablyprofound.

Repugnancemaybetheonlyvoiceleftthatspeaksuptodefendthecentralcoreofhumanity LeonKass

O f d U hi C t f P ti l Ethi


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WhatisHumanity?

Distinguishesusfromotheranimals

Notbiology

Share98.5%ofgenomewithchimps

MuchofourDNAisviral

Candidatepropertiesforourmoralstatus[PropertyX]

capacitytoreason

capacitytoactfromnormativereasons,includingmoralreasons

capacitytoactautonomously

capacityto

engage

in

complex

social

relationships

capacitytodisplayempathyandsympathy

capacitytohavefaith(believeinagod)

O ford Uehiro Centre for Practical Ethics


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WhatPromotesorErodesOurHumanity?

Actionswhichexpressourhumanity

Expressourpracticalrationality

Modificationtopreventdiseasevs creationoffreaksfor

entertainment Pigvalvesusedinsurgery

Xenotransplants

Piginsulin



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HumanChimeras

Possiblereasons

Eugenic

SourceofEScells

Infertilitytreatment


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TheMoralStatusofChimeras

Mouse/ratwithbrainmadefromhumanembryonicstemcells

StudyHuntingtonDisease,AlzheimerDisease

Doesit

have

Property

X?



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MoralStatus

PropertyXcanbepromotedoreroded

Actionswhicherodeorpromotethecapacitytoengageinpracticalreasoning

Improvedsensorycapacity,longevity,empathy,rationality,memoryvs ferociousness,violence



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Conclusion

Radicalgeneticalterationofhumansisnotnecessarilyathreattoourhumanity

Itmaybe

Butitmaypromoteourhumanity

Anotherlesson:

Candoesnotimplywill

Againsttheempiricalversionoftheslipperyslope

argument



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MoralResponsibility

Oughtimpliescan

Whenwecouldnotaffectthebiologicalnatureofhumanbeings,wewerenotresponsiblefortheirdeficienciesanddisabilities

Can(roughly)impliesoughttodecide

Whenwecaninfluencebiology,wearemorallyresponsiblefortheforeseeableconsequencesoffailingtointervene/leavingittonature

Wecanbemorallyresponsiblefortheforeseeableconsequencesofouromissions sinsofomission


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Methods

(1)soundanalyticphilosophy;

(2)interdisciplinarycollaborationwithotherresearchersinthehumanitiesandsciencesandtheuseofrelevantempiricalresearchfromthose

disciplines;

(3)seamlesscollaborationwithscientistsandmedicalprofessionalsinvolvedinthedevelopmentoftechnologytoidentifyethicalissuesarisingfromimminentandlongtermdevelopments.



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PracticalEthicsinOxford

workisbothproactiveaswellasreactive.

constructiveaswellasobstructive

itidentifiesstrategiestofacilitategoodscientificdevelopment

aswell

as

identifying

the

limits

to

research

and

development

oftheseareasofscience.



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ConvergingTechnologies:NBIC

Nanotechnology

Biotechnology

Informationtechnology

CognitiveScience



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DutchResearchCouncil

researchprogramontheethicsoftechnology(10MillionEurofor4years)incollaborationwithotherMinisteries andpublicpolicymakers

(1)inter/multidisciplinarycollaboration(eachprojectunderthis

program

has

to

demonstrate

effective

collaboration

between

scientists/engineers,ethicists,andsocialorbehaviouralscientists)

(2)anticipatoryethicsshouldkickinpreferrably whenitcanstillmakeadifference

(3)focusondesign(genes,molecules,devices,systems,infrastructure)insteadofexclusivelyonanalysisandevaluation

(4)researchshouldbeinternational

new technologies and human enhancement

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