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