02 dr. james sherley biotechnology cloning nano technology s
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Biotechnology and the FamilyBiotechnology and the FamilyCloning, Genetic Engineering, andCloning, Genetic Engineering, and
NanotechnologyNanotechnology
James L. Sherley, M.D., Ph.D.James L. Sherley, M.D., Ph.D.Associate Professor of Biological EngineeringAssociate Professor of Biological Engineering
Biological Engineering DivisionBiological Engineering DivisionMassachusetts Institute of TechnologyMassachusetts Institute of TechnologyBiotechnology Process Engineering CenterBiotechnology Process Engineering CenterCenter for Environmental Health ScienceCenter for Environmental Health Science
Center for Cancer ResearchCenter for Cancer Research
OUTLINEOUTLINE
•The origins of technologyThe origins of technology•Impact of technology on the humanImpact of technology on the human
familyfamily•Nano-, Geno-, Bio-technologyNano-, Geno-, Bio-technology•Human stem cell biologyHuman stem cell biology•Biotechnology and the human embryoBiotechnology and the human embryo•Moral and ethical challengesMoral and ethical challenges
ScienceScience:: the human process of discovery the human process of discovery
From birth, all humans practice science.From birth, all humans practice science.
Seeking knowledge and understanding ofSeeking knowledge and understanding ofthe world is instinctive in human beings.the world is instinctive in human beings.
We don’t learn how to do it; we know howWe don’t learn how to do it; we know howto do it.to do it.
So, what makes a So, what makes a scientistscientist??
So, what makes a So, what makes a scientistscientist??
Motivation to discover that which isMotivation to discover that which isunknown.unknown.
INCREASE KNOWLEDGE AND INCREASE KNOWLEDGE AND UNDERSTANDING OF THE WORLD,UNDERSTANDING OF THE WORLD,INCLUDING OURSELVES, HUMANINCLUDING OURSELVES, HUMANBEINGS BEINGS
TechnologyTechnology is the application of human is the application of humanknowledge.knowledge.
TechnologyTechnology is the application of human is the application of humanknowledge.knowledge.
But, to what end?But, to what end?
Good ends?Good ends?
Improve the human experience; improveImprove the human experience; improvethe quality of life the quality of life forfor allall ideally ideally
- the engineer’s creed- the engineer’s creed
MedicineMedicine ManufacturingManufacturingBuildingBuilding CommunicationCommunicationFoodFood EducationEducationEntertainmentEntertainment TravelTravel
Bad ends?Bad ends?
Improve the quality of life Improve the quality of life for only somefor only some;;Imperialism, conquest, destruction,Imperialism, conquest, destruction,oppressionoppression
WeaponsWeapons EnvironmentEnvironmentToxinsToxins Disease (Disease (e.g.,e.g., lung cancer) lung cancer)
“ “Prometheus’s Gift”Prometheus’s Gift”
SCIENCESCIENCE TECHNOLOGYTECHNOLOGY SOCIETYSOCIETY
“ “Pandora’s Box”Pandora’s Box”
“ “Prometheus’s Gift”Prometheus’s Gift”
SCIENCESCIENCE TECHNOLOGYTECHNOLOGY SOCIETYSOCIETY
“ “Pandora’s Box”Pandora’s Box”
“ “Prometheus’s Gift”Prometheus’s Gift”
SCIENCESCIENCE TECHNOLOGYTECHNOLOGY SOCIETYSOCIETY
“ “Pandora’s Box”Pandora’s Box”
SOCIETY is the HUMAN FAMILYSOCIETY is the HUMAN FAMILYTECHNOLOGY’S IMPACTTECHNOLOGY’S IMPACTBefore: the nature of livingBefore: the nature of living
“ “Prometheus’s Gift”Prometheus’s Gift”
SCIENCESCIENCE TECHNOLOGYTECHNOLOGY SOCIETYSOCIETY
“ “Pandora’s Box”Pandora’s Box”
SOCIETY is the HUMAN FAMILYSOCIETY is the HUMAN FAMILYTECHNOLOGY’S IMPACTTECHNOLOGY’S IMPACTBefore: the nature of livingBefore: the nature of living
Now: Biotechnology questions the veryNow: Biotechnology questions the verynature of human lifenature of human life
NanotechnologyNanotechnologyManipulation of biomaterials and physicalManipulation of biomaterials and physicalmaterials at a nanoscale.materials at a nanoscale.
GenotechnologyGenotechnology (genetic engineering) (genetic engineering)Manipulation of genes, DNA sequencesManipulation of genes, DNA sequencesthat encode the functions of lifethat encode the functions of life
BiotechnologyBiotechnologyManipulation of Manipulation of cellscells; encompasses; encompassesnanotechnology and genotechnologynanotechnology and genotechnology
NanotechnologyNanotechnologyManipulation of biomaterials and physicalManipulation of biomaterials and physicalmaterials at a nanoscale.materials at a nanoscale.
Nanoscale ~ about the size of a particle from dividingNanoscale ~ about the size of a particle from dividing up a grain of sand into a million piecesup a grain of sand into a million pieces ((i.ei.e., a nanometer in diameter)., a nanometer in diameter)
Nanotechnology ApplicationsNanotechnology Applications
Building up materials from such small units canBuilding up materials from such small units canspeed up manufacturing and make materials withspeed up manufacturing and make materials withnovel properties (novel properties (e.ge.g., increased strength)., increased strength)
Nanoscale surfaces have novel interaction propertiesNanoscale surfaces have novel interaction properties
New methods for imaging single moleculesNew methods for imaging single molecules
New devices for more efficient controlled drug deliveryNew devices for more efficient controlled drug delivery
SAFE?SAFE?
Genotechnology ApplicationsGenotechnology Applications
Genetically modified organisms (GMO’s)Genetically modified organisms (GMO’s)
Gene therapy - problemsGene therapy - problems
Genetic testing, pre-implantation genetic diagnosisGenetic testing, pre-implantation genetic diagnosis(PGD)(PGD)
[Eugenics - amniocentesis, PGD embryonic deaths][Eugenics - amniocentesis, PGD embryonic deaths]
SAFE?SAFE?
Genotechnology ApplicationsGenotechnology Applications
Genetically modified organisms (GMO’s)Genetically modified organisms (GMO’s)
Gene therapy - problemsGene therapy - problems
Genetic testing, pre-implantation genetic diagnosisGenetic testing, pre-implantation genetic diagnosis(PGD)(PGD)
[Eugenics - amniocentesis, PGD embryonic deaths][Eugenics - amniocentesis, PGD embryonic deaths]
SAFE?SAFE? MORAL?MORAL?
Genotechnology ApplicationsGenotechnology Applications
Genetically modified organisms (GMO’s)Genetically modified organisms (GMO’s)
Gene therapy - problemsGene therapy - problems
Genetic testing, pre-implantation genetic diagnosisGenetic testing, pre-implantation genetic diagnosis(PGD)(PGD)
[Eugenics - amniocentesis, PGD embryonic deaths][Eugenics - amniocentesis, PGD embryonic deaths]
SAFE?SAFE? MORAL?MORAL?Natural errors; prevent hardshipNatural errors; prevent hardship
The Biotechnology of ReproductionThe Biotechnology of Reproduction
Artificial insemination (sperm transfer)Artificial insemination (sperm transfer)
In vitro fertilization (sperm and egg in glass)In vitro fertilization (sperm and egg in glass)Human embryonic stem cell researchHuman embryonic stem cell research
Human CloningHuman Cloning
SAFE?SAFE?
The Biotechnology of ReproductionThe Biotechnology of Reproduction
Artificial insemination (sperm transfer)Artificial insemination (sperm transfer)
In vitro fertilization (sperm and egg in glass)In vitro fertilization (sperm and egg in glass)Human embryonic stem cell researchHuman embryonic stem cell research
Human CloningHuman Cloning
SAFE?SAFE? ETHICAL?ETHICAL? MORAL?MORAL?
The Biotechnology of ReproductionThe Biotechnology of Reproduction
Artificial insemination (sperm transfer)Artificial insemination (sperm transfer)
In vitro fertilization (sperm and egg in glass)In vitro fertilization (sperm and egg in glass)Human embryonic stem cell researchHuman embryonic stem cell research
Human CloningHuman Cloning
SAFE?SAFE? ETHICAL?ETHICAL? MORAL?MORAL?WHAT IS HUMAN?WHAT IS HUMAN?
BIOTECHNOLOGY - CELL BIOLOGYBIOTECHNOLOGY - CELL BIOLOGY
Potten et al., 2003
CELLS:CELLS:MICRO-SCALEMICRO-SCALE1/100 OF A GRAIN OF SAND1/100 OF A GRAIN OF SANDTrillions in the human bodyTrillions in the human body
Organs and TissuesOrgans and Tissues
Cells are Complex (micro-, nano- )Cells are Complex (micro-, nano- )
mitochondrionmitochondrion(DNA)(DNA)
lysosomelysosome
vacuole/vesiclevacuole/vesicle
endoplasmicendoplasmicreticulumreticulum
golgigolgi
NucleusNucleusDNADNA
GENETIC MATERIALGENETIC MATERIAL
ribosomesribosomesRNARNA
Protein SynthesisProtein Synthesis
Cells are EnginesCells are Engines
WorkWorkMoveMoveMorphMorphSecreteSecreteSynthesizeSynthesizeInduce CurrentInduce CurrentHold ChargeHold ChargeTransform ChemicalsTransform Chemicals
HeatHeat
ChemicalChemicalEnergyEnergy
The Special Work of Life: Self-DuplicationThe Special Work of Life: Self-Duplication
““Cell Division”Cell Division”
2n2n 2n2n
G1G1
4n4n
SSDNADNA
SSYNTHESISYNTHESIS
4n4n
2n2n
2n2nG2G2 MM
(n = parental complement of DNA)(n = parental complement of DNA)
Cell Hierarchy of Human DevelopmentCell Hierarchy of Human Development
Embryonic cellsEmbryonic cells - divide, change, form the body - divide, change, form the body
Adult stem cellsAdult stem cells - divide, don’t change, replace - divide, don’t change, replacespecific types of mature cellsspecific types of mature cells
Mature specified cellsMature specified cells - some divide, many don’t divide, - some divide, many don’t divide,perform specialized functionsperform specialized functions
© 2001 Terese Winslow, Caittlin Duckwall© 2001 Terese Winslow, Caittlin Duckwall
Embryonic CellsEmbryonic Cells
Adult Stem CellsAdult Stem Cells Mature Cells Mature Cells
Cell HierarchyCell Hierarchyofof
HumanHumanDevelopment Development
AsymmetricAsymmetricSelf-RenewalSelf-Renewal
SymmetricSymmetricDivisionsDivisions
DifferentiationDifferentiation
Terminal ArrestTerminal Arrest
DeathDeath
Adult Stem CellsAdult Stem Cells
Adult Stem CellsAdult Stem Cells– – responsible for renewal of mature tissueresponsible for renewal of mature tissue cells by asymmetric self-renewalcells by asymmetric self-renewal
© 2001 Terese Winslow, Caittlin Duckwall© 2001 Terese Winslow, Caittlin Duckwall
Embryonic Stem CellsEmbryonic Stem Cells
““Treat All Adult Tissues!”Treat All Adult Tissues!”
Adult Stem CellsAdult Stem Cells
Stem CellsStem CellsForFor
Biomedicine Biomedicine
Two Main Types of Stem Cells
1) Embryonic
Derived from embryos
“Easily” identified and isolated
Pluripotent (“treat all tissues”)
Easy to grow
Problems
Moral and ethical issues
Form tumors
2) Adult
Derived from adult tissues
No identifiers and hard to isolate
Multipotent or unipotent
Hard to grow
Solutions
Informed consent possible
Do not form tumors
Sources of Human Embryonic Stem Cells
1. In Vitro Fertilization (IVF)sperm + egg = IVF embryo (complete nucleus)
IVF embryo dissociate = ES cell culture (PGD Approach?)
2. Somatic Cell Nuclear Transplantation (SCNT) “Therapeutic Cloning”
egg - incomplete nucleus = enucleated eggenucleated egg + complete nucleus = cloned embryocloned embryo dissociate = ES cell culture
3. Genetically-engineered SCNT - Defective Embryos“Altered Nuclear Transplantation;” “Oocyte-Assisted Re-programming”
4. Human-Animal Chimera Embryos (Human DNA)!!??
CLEAR DILEMMAS FOR THE HUMAN FAMILYCLEAR DILEMMAS FOR THE HUMAN FAMILY
MoralMoralHuman embryos are living human beings.Human embryos are living human beings.Shall we destroy them for the potential gain of others?Shall we destroy them for the potential gain of others?
EthicalEthicalHuman embryos cannot consent to their sacrifice.Human embryos cannot consent to their sacrifice.Egg donor recruitment and treatmentEgg donor recruitment and treatment““Fetal-farming” for eggsFetal-farming” for eggs
Are the promises of human embryonic stem cellAre the promises of human embryonic stem cellresearch valid, plausible?research valid, plausible?
DEFINING LIVINGDEFINING LIVING
EnergyEnergy SelfSelfDuplicationDuplication
SunlightSunlightOrganicOrganic
MoleculesMolecules
DEFINING HUMAN BEINGSDEFINING HUMAN BEINGS
≠≠
SomaticSomaticCellCell
ZygoteZygoteSingle-cellSingle-cell
EmbryoEmbryo
EggEgg
EnucleatedEnucleated EggEgg
DEFINING HUMAN BEINGSDEFINING HUMAN BEINGS
SpermSperm
Somatic CellSomatic CellNucleusNucleus
Natural Fertilization;Natural Fertilization;In VitroIn Vitro Fertilization (IVF) Fertilization (IVF)
Somatic Cell NuclearSomatic Cell NuclearTransplantation (SCNT)Transplantation (SCNT)
DEFINING HUMAN BEINGSDEFINING HUMAN BEINGS
Zygotes - Zygotes - Pre-development, Living,Pre-development, Living,Single-cell Human BeingSingle-cell Human BeingActivated Human GenomeActivated Human Genome
Natural Fertilization;Natural Fertilization;In VitroIn Vitro Fertilization (IVF) Fertilization (IVF)
Somatic Cell NuclearSomatic Cell NuclearTransplantation (SCNT)Transplantation (SCNT)
CLEAR DILEMMAS FOR THE HUMAN FAMILYCLEAR DILEMMAS FOR THE HUMAN FAMILY
MoralMoralHuman embryos are living human beings.Human embryos are living human beings.Shall we destroy them for the potential gain of others?Shall we destroy them for the potential gain of others?
EthicalEthicalHuman embryos cannot consent to their sacrifice.Human embryos cannot consent to their sacrifice.Egg donor recruitment and treatmentEgg donor recruitment and treatment““Fetal-farming” for eggsFetal-farming” for eggs
Are the promises of human embryonic stem cellAre the promises of human embryonic stem cellresearch valid, plausible?research valid, plausible?
AsymmetricAsymmetricSelf-RenewalSelf-Renewal
SymmetricSymmetricDivisionsDivisions
DifferentiationDifferentiation
Terminal ArrestTerminal Arrest
DeathDeath
Adult Stem CellsAdult Stem Cells
““Embryonic stem cells cannot beEmbryonic stem cells cannot be used to treat adult tissues.”used to treat adult tissues.”
1.1. Tumor formationTumor formation
2.2. Change whenChange whenproducing matureproducing maturecellscells
2.2. No asymmetricNo asymmetricself-renewalself-renewal
WHAT?!
““Scientists will be scientists.”Scientists will be scientists.”andand““Technologists will be technologists.”Technologists will be technologists.”
Motivation to discover that which isMotivation to discover that which isunknown.unknown.
Motivation to make something “useful.”Motivation to make something “useful.”
“ “Prometheus’s Gift”Prometheus’s Gift”
SCIENCESCIENCE TECHNOLOGYTECHNOLOGY SOCIETYSOCIETY
“ “Pandora’s Box”Pandora’s Box”
HUMANHUMANFAMILYFAMILY
“ “Prometheus’s Gift”Prometheus’s Gift”
SCIENCESCIENCE TECHNOLOGYTECHNOLOGY SOCIETYSOCIETY
“ “Pandora’s Box”Pandora’s Box”
HONEST, COMPLETEHONEST, COMPLETEDISCLOSUREDISCLOSURE
HUMANHUMANFAMILYFAMILY