UNIVERSCITY OCF PENNSYLVANIA CENTER FOR ......California Proposition 71: “Stem Cell Research and...

Ethics and Regulation

of Human Embryonic

Stem Cell Research

Ethics and Regulation

of Human Embryonic

Stem Cell Research

Jonathan D. Moreno

David and Lyn Silfen University ProfessorDat

UNIVERSCITY OCF PENNSYLVANIA

CENTER FOR BIOETHICS

Why are doctors and scientists Why are doctors and scientists

excited about the use of stem cells excited about the use of stem cells

in therapy?in therapy?

�� Drug developmentDrug development

�� Basic researchBasic research

�� REGENERATIVE MEDICINEREGENERATIVE MEDICINE

•• Adult stem cellsAdult stem cells

•• Embryonic stem cellsEmbryonic stem cells

““AdultAdult”” stem cellsstem cells

�� 1. 1. HematapoieticHematapoietic--Form all types of blood Form all types of blood

cellscells

�� 2. 2. StromalStromal--Form bone, cartilage, fat, and Form bone, cartilage, fat, and

fibrous connective tissuefibrous connective tissue

�� 3. Brain3. Brain--brain and skeletal musclebrain and skeletal muscle

But adult stem cells are few in number, hard to But adult stem cells are few in number, hard to

find, hard to purify, and donfind, hard to purify, and don’’t seem to be able t seem to be able

to become many different kinds of cellto become many different kinds of cell

Embryonic stem cellsEmbryonic stem cells

�� First isolated in 1998First isolated in 1998

�� Are Are ““pluripotentpluripotent””——can become all of can become all of

the bodythe body’’s 200+ cell typess 200+ cell types

�� Can divide many times and keep Can divide many times and keep

their their pluripotencypluripotency, becoming , becoming ““cell cell

lineslines””

Somatic Cell Nuclear TransferSomatic Cell Nuclear Transfer

Guidelines for Human Embryonic Guidelines for Human Embryonic

Stem Cell ResearchStem Cell Research

Summary of a report, recommendations and guidelines by the NatioSummary of a report, recommendations and guidelines by the National nal Research Council of the National Academies, Research Council of the National Academies,

April 26, 2005April 26, 2005

Richard O Hynes (MIT) and Jonathan D. Moreno (Richard O Hynes (MIT) and Jonathan D. Moreno (UVaUVa), co), co--chairschairs

�� CoCo--sponsored by NAS and Institute of Medicinesponsored by NAS and Institute of Medicine

�� Not government agencies, chartered by federal governmentNot government agencies, chartered by federal government

�� Reports have only intellectual suasionReports have only intellectual suasion

�� This project supported by two foundations (This project supported by two foundations (GreenwallGreenwall and Ellison), and and Ellison), and internal NAS fundsinternal NAS funds

In 2002, the NAS recommended both adult and embryonic stem cell In 2002, the NAS recommended both adult and embryonic stem cell research research should proceedshould proceed

Committee MembersCommittee Members

Elizabeth Price FoleyElizabeth Price Foley, Professor of Law; Florida International University , Professor of Law; Florida International University College of LawCollege of Law

Norman C. FostNorman C. Fost, Professor of Pediatrics; Director of the Program in Medical , Professor of Pediatrics; Director of the Program in Medical Ethics; University of WisconsinEthics; University of Wisconsin

H. Robert HorvitzH. Robert Horvitz, Professor of Biology; Investigator, Howard Hughes , Professor of Biology; Investigator, Howard Hughes Medical School, Massachusetts Institute of TechnologyMedical School, Massachusetts Institute of Technology

Marcia Marcia ImbresciaImbrescia, , Trustee, Arthritis FoundationTrustee, Arthritis Foundation

Terry Magnuson,Terry Magnuson, Sarah Graham Sarah Graham KenanKenan Professor and Chair of Genetics; Professor and Chair of Genetics; Director, Carolina Center for Genome Sciences; University of NorDirector, Carolina Center for Genome Sciences; University of North th CarolinaCarolina

Cheryl Cheryl MwariaMwaria, Associate Professor of Anthropology; , Associate Professor of Anthropology; HofstraHofstra UniversityUniversity

Janet Janet RossantRossant, Joint Head; Program in Development and Fetal Health; , Joint Head; Program in Development and Fetal Health; Samuel Samuel LunenfeldLunenfeld Research Institute; Mount Sinai Hospital, Toronto, Research Institute; Mount Sinai Hospital, Toronto, CanadaCanada

Janet RowleyJanet Rowley, Blum, Blum--RieseRiese Distinguished Service Professor of Medicine; Distinguished Service Professor of Medicine; Section of Section of HaematologyHaematology/Oncology; University of Chicago Medical Center/Oncology; University of Chicago Medical Center

Alta CharoAlta Charo, Elizabeth S. Wilson, Elizabeth S. Wilson--BascomBascom Professor of Law and Bioethics, Professor of Law and Bioethics, University of Wisconsin (Liaison from Board of Life Sciences) University of Wisconsin (Liaison from Board of Life Sciences)

Bush Administration PolicyBush Administration Policy

�� Federally funded research only Federally funded research only

permissible on stem cell lines derived permissible on stem cell lines derived

before 9 pm on August 9, 2001before 9 pm on August 9, 2001

Approved coloniesApproved coloniesBresaGenBresaGen, Inc.,, Inc., Athens, GeorgiaAthens, Georgia 44

CyTheraCyThera, Inc.,, Inc., San Diego, CaliforniaSan Diego, California 99

ES Cell International,ES Cell International, Melbourne, AustraliaMelbourne, Australia 66

GeronGeron, Inc.,, Inc., Menlo Park, CaliforniaMenlo Park, California 77

GGööteborgteborg University,University, GGööteborgteborg, Sweden, Sweden 1919

KarolinskaKarolinska Institute,Institute, Stockholm, SwedenStockholm, Sweden 66

National Centre for Biological Sciences/ Tata National Centre for Biological Sciences/ Tata

Institute of Fundamental Research,Institute of Fundamental Research,

Bangalore, IndiaBangalore, India 33

Reliance Life Sciences,Reliance Life Sciences, Mumbai, IndiaMumbai, India 77

TechnionTechnion University,University, Haifa, IsraelHaifa, Israel 44

University of California,University of California, San Francisco, San Francisco,

CaliforniaCalifornia 22

WWisconsin Alumni Researchisconsin Alumni Research Foundation,Foundation,

Madison, WisconsinMadison, Wisconsin 55

Stem cell research in US Stem cell research in US

since 9 August 2001since 9 August 2001�� $28 million dollars in grants awarded $28 million dollars in grants awarded by NIHby NIH

�� 22 NIH lines available22 NIH lines available

�� Patent issues constrain access to Patent issues constrain access to lineslines

�� Lines hard to grow and transportLines hard to grow and transport

�� Researchers hesitate to enter fieldResearchers hesitate to enter field

�� >120 lines available in US and >120 lines available in US and elsewhere from private sourceselsewhere from private sources

California Proposition 71:California Proposition 71:““Stem Cell Research and Cures InitiativeStem Cell Research and Cures Initiative””

�� Establishes "California Institute for Regenerative Medicine" Establishes "California Institute for Regenerative Medicine" to regulate stem cell research and provide funding, through to regulate stem cell research and provide funding, through grants and loans, for such research and research facilities. grants and loans, for such research and research facilities.

�� Establishes constitutional right to conduct stem cell Establishes constitutional right to conduct stem cell research; prohibits Institute's funding of human research; prohibits Institute's funding of human reproductive cloning research. reproductive cloning research.

�� Establishes oversight committee to govern Institute. Establishes oversight committee to govern Institute.

�� Provides General Fund loan up to $3 million for Institute's Provides General Fund loan up to $3 million for Institute's initial administration/implementation costs. initial administration/implementation costs.

�� Authorizes issuance of general obligation bonds to finance Authorizes issuance of general obligation bonds to finance Institute activities up to $3 billion subject to annual limit ofInstitute activities up to $3 billion subject to annual limit of$350 million. $350 million.

�� Appropriates monies from General Fund to pay for bonds. Appropriates monies from General Fund to pay for bonds.

Other Current State ActivityOther Current State Activity

�� Funding* provided in Funding* provided in

•• CaliforniaCalifornia

•• WisconsinWisconsin

•• ConnecticutConnecticut

•• New JerseyNew Jersey

•• IllinoisIllinois

•• MarylandMaryland

•• ConnecticutConnecticut

�� Missouri Research and Cures bill protects privately funded Missouri Research and Cures bill protects privately funded researchresearch

�� New York plans on $600 million for stem cell researchNew York plans on $600 million for stem cell research

�� Possible initiatives in Florida, Kansas, MichiganPossible initiatives in Florida, Kansas, Michigan

�� Ongoing debate in Texas, VirginiaOngoing debate in Texas, Virginia

*Center for American Progress, *Center for American Progress, ““Too Much to Ask,Too Much to Ask,”” 2006, 2006, http://images1.americanprogress.org/il80web20037/cap/Statehttp://images1.americanprogress.org/il80web20037/cap/StatestemCellReport.pdfstemCellReport.pdf

The Need for GuidelinesThe Need for Guidelines

�� hEShES cell research already actively underway cell research already actively underway with both federal and nonwith both federal and non--federal funding federal funding --several states are initiating major research several states are initiating major research effortsefforts

�� Significant public support for Significant public support for hEShES cell cell researchresearch

�� A patchwork of regulationsA patchwork of regulations•• Limited federal support / little federal regulationLimited federal support / little federal regulation

•• No federal regulations governing No federal regulations governing hEShES cell research cell research funded from other sourcesfunded from other sources

•• Disparate state regulationsDisparate state regulations

�� No system for oversight of No system for oversight of hEShES cell researchcell research

�� Uncertainty about appropriate proceduresUncertainty about appropriate procedures•• Public concernsPublic concerns

•• Uncertain scientific environment Uncertain scientific environment

Guidelines for Human Embryonic Stem Cell Research

Issues ConsideredIssues Considered

1)1) Recruitment of donors of Recruitment of donors of blastocystsblastocysts, gametes, or somatic , gametes, or somatic cellscells

informed consentinformed consent

financial incentivesfinancial incentives

conflicts of interestconflicts of interest

donor confidentialitydonor confidentiality

risks associated with risks associated with oocyteoocyte retrievalretrieval

handling of genetic information arising from the researchhandling of genetic information arising from the research

2)2) Characterization and standardization of stem cellsCharacterization and standardization of stem cells

3)3) Safe handling and storage of Safe handling and storage of blastocystsblastocysts and stem cell and stem cell material material

4)4) Conditions for transfer of such material among laboratoriesConditions for transfer of such material among laboratories

5)5) Appropriate uses of Appropriate uses of hEShES cells in research or therapy cells in research or therapy

6)6) Limitations on the use of Limitations on the use of hEShES cellscells

7) 7) Safeguards against misuseSafeguards against misuse


NATIONAL ACADEMIES GUIDELINES FOR RESEARCH NATIONAL ACADEMIES GUIDELINES FOR RESEARCH

ON HUMAN EMBRYONIC STEM CELLSON HUMAN EMBRYONIC STEM CELLS

�� 1.0 1.0 IntroductionIntroduction

�� 2.0 2.0 Establishment of an Institutional Embryonic Establishment of an Institutional Embryonic Stem Cell Research Oversight CommitteeStem Cell Research Oversight Committee

�� 3.03.0 Procurement of Gametes, Procurement of Gametes, BlastocystsBlastocysts or Cells or Cells for for hEShES GenerationGeneration

�� 4.04.0 Derivation of Derivation of hEShES Cell LinesCell Lines

�� 5.05.0 Banking and Distribution of Banking and Distribution of hEShES Cell LinesCell Lines

�� 6.06.0 Research Use of Research Use of hEShES Cell LinesCell Lines

�� 7.07.0 International CollaborationInternational Collaboration

�� 8.08.0 Conclusion and Need for a National PanelConclusion and Need for a National Panel


These guidelines cover all derivation of These guidelines cover all derivation of hEShES cell lines and all cell lines and all

research that uses research that uses hEShES cells derived from cells derived from

(1) (1) BlastocystsBlastocysts made for reproductive purposes and later made for reproductive purposes and later

obtained for research from in vitro fertilization (IVF) clinics.obtained for research from in vitro fertilization (IVF) clinics.

(2) (2) BlastocystsBlastocysts made specifically for research using IVF.made specifically for research using IVF.

(3) Somatic cell nuclear transfer (NT) into (3) Somatic cell nuclear transfer (NT) into oocytesoocytes..


1.1(a) What The Guidelines Cover1.1(a) What The Guidelines Cover

Many, but not all, of the guidelines and concerns are common to other areas

of human stem cell research, such as(a) Research that uses human adult stem cells.(b) Research that uses fetal stem cells or

embryonic germ cells derived from fetal tissue

1.1(b) Reproductive Uses of Nuclear Transfer 1.1(b) Reproductive Uses of Nuclear Transfer

The guidelines do not address reproductive uses of The guidelines do not address reproductive uses of

nuclear transfer nuclear transfer -- those are addressed in the 2002 those are addressed in the 2002

report report Scientific and Medical Aspects of Human Scientific and Medical Aspects of Human

Reproductive CloningReproductive Cloning, in which the National , in which the National

Academies recommended that Academies recommended that ““Human Human

reproductive cloning should not now be practiced. reproductive cloning should not now be practiced.

It is dangerous and likely to fail.It is dangerous and likely to fail.””

Although the guidelines do not specifically address Although the guidelines do not specifically address

human reproductive cloning, it continues to be the human reproductive cloning, it continues to be the

view of the National Academies that research view of the National Academies that research

aimed at the aimed at the reproductive cloning of a human being reproductive cloning of a human being

should not be conducted should not be conducted at this time.at this time.Guidelines for Human Embryonic Stem Cell Research

�� Should always be reviewed by an Institutional Review BoardShould always be reviewed by an Institutional Review Board

�� Should be governed by informed consent of Should be governed by informed consent of allall donorsdonors

�� Separation of decision to donate from all clinical decisionsSeparation of decision to donate from all clinical decisions

�� No payments to donors beyond reimbursement No payments to donors beyond reimbursement

of direct expensesof direct expenses

�� No purchase or sale of donated materialsNo purchase or sale of donated materials

�� Protection of donor privacyProtection of donor privacy


Donations of Donations of blastocystsblastocysts, , oocytesoocytes, ,

sperm and somatic cellssperm and somatic cells

Functions of Embryonic Stem Cell Research Oversight Functions of Embryonic Stem Cell Research Oversight

(ESCRO) Committees (ESCRO) Committees -- #1#1

�� To provide local oversight over all issues To provide local oversight over all issues related to derivation and research use of related to derivation and research use of hEShEScell lines cell lines

�� To ensure adherence to the basic ethical and To ensure adherence to the basic ethical and legal principles of informed consent and legal principles of informed consent and protection of donor confidentiality. protection of donor confidentiality.

�� To review compliance of all To review compliance of all hEShES cell research cell research with all relevant regulations and guidelines.with all relevant regulations and guidelines.

�� To maintain registries of To maintain registries of hEShES cell research cell research conducted at the institution and of all conducted at the institution and of all hEShES cell cell lineslines


Functions ofFunctions of Embryonic Stem Cell Research Embryonic Stem Cell Research

Oversight Oversight

(ESCRO) Committees (ESCRO) Committees -- #2#2

�� To facilitate education of investigators involved To facilitate education of investigators involved in in hEShES cell research cell research

�� The ESCRO committee will not substitute for an The ESCRO committee will not substitute for an Institutional Review Board (IRB) but rather will Institutional Review Board (IRB) but rather will provide an additional level of review and provide an additional level of review and scrutiny warranted for scrutiny warranted for hEShES cell research and cell research and review proposals not requiring IRB review. review proposals not requiring IRB review.

�� To review and approve the scientific merit of To review and approve the scientific merit of research proposals and divide into three research proposals and divide into three categories in setting limits on research and categories in setting limits on research and determining the requisite level of oversight:determining the requisite level of oversight:


Permissible Research without Permissible Research without

Further ReviewFurther Review

Some Some hEShES cell research is cell research is

permissible after notification of permissible after notification of

the ESCRO committee and the ESCRO committee and

completion of all reviews completion of all reviews

mandated by current mandated by current

requirements; e.g., all purely requirements; e.g., all purely in in

vitrovitro hEShES cell research with precell research with pre--

existing coded or anonymous existing coded or anonymous

hEShES cell lines.cell lines.

Research that is Only Permissible Research that is Only Permissible

with Further Review and Approvalwith Further Review and Approval

(i) all derivations of new (i) all derivations of new hEShES cell lines from donated cell lines from donated blastocystsblastocysts, from in vitro fertilized , from in vitro fertilized oocytesoocytes, or by , or by nuclear transfer.nuclear transfer.

(ii) all research involving the introduction of (ii) all research involving the introduction of hEShEScells into nonhuman animals at any stage of cells into nonhuman animals at any stage of embryonic, fetal, or postnatal development.embryonic, fetal, or postnatal development.

(iii) all research in which identifiable information (iii) all research in which identifiable information about donors is about donors is readily ascertainable or could readily ascertainable or could become known by the investigatorbecome known by the investigator

(i) Research involving (i) Research involving in vitroin vitro culture of any intact culture of any intact human embryo, regardless of derivation method, for human embryo, regardless of derivation method, for longer than 14 days or until formation of the primitive longer than 14 days or until formation of the primitive streak begins, whichever occurs first.streak begins, whichever occurs first.

(ii) Research in which (ii) Research in which hEShES cells are introduced into cells are introduced into nonhuman primate nonhuman primate blastocystsblastocysts or in which any ES cells or in which any ES cells are introduced into human are introduced into human blastocystsblastocysts..

(iii) No animal into which (iii) No animal into which hEShES cells have been cells have been introduced at any stage of development should be introduced at any stage of development should be allowed to breed.allowed to breed.


Research that should not be Research that should not be

permitted at this timepermitted at this time

Recommendations for Oversight of Human Recommendations for Oversight of Human

Embryonic Stem (Embryonic Stem (hEShES) Cell Research) Cell Research

1. Local oversight1. Local oversight -- each institution should establish each institution should establish

an Embryonic Stem Cell Research Oversight an Embryonic Stem Cell Research Oversight

(ESCRO) committee to review and monitor all (ESCRO) committee to review and monitor all

proposals to conduct proposals to conduct hEShES cell research. cell research.

The committee should include representatives of the The committee should include representatives of the

public and persons with expertise in developmental public and persons with expertise in developmental

biology, stem cell research, molecular biology, assisted biology, stem cell research, molecular biology, assisted

reproduction, and ethical and legal issues in reproduction, and ethical and legal issues in hEShES cell cell

research. research.


2. A national panel should be established to assess

periodically the adequacy of the guidelines and to

provide a forum for a continuing discussion of issues involved in hES cell research.

�� Regulations based on these guidelines have been adopted by the Regulations based on these guidelines have been adopted by the California Institute for Regenerative Medicine (CIRM) California Institute for Regenerative Medicine (CIRM)

�� The Commonwealth of Massachusetts has enacted legislation with The Commonwealth of Massachusetts has enacted legislation with nearly identical requirementsnearly identical requirements

�� They have been adopted and/or endorsed by a number of science They have been adopted and/or endorsed by a number of science organizations and universities including: organizations and universities including:

•• Association of American Medical CollegesAssociation of American Medical Colleges

•• Association of American UniversitiesAssociation of American Universities

•• Federation of American Societies for Experimental BiologyFederation of American Societies for Experimental Biology

•• Society for Developmental BiologySociety for Developmental Biology

•• University of CaliforniaUniversity of California

•• American Society for Cell BiologyAmerican Society for Cell Biology

•• President of the Massachusetts Institute of TechnologyPresident of the Massachusetts Institute of Technology

•• Provosts of Harvard University, Yale University, Princeton UniveProvosts of Harvard University, Yale University, Princeton University, rsity, the University of Chicago, the Massachusetts Institute of Technothe University of Chicago, the Massachusetts Institute of Technology logy and Cornell Universityand Cornell University

CIRM Regulations (9/2/06)CIRM Regulations (9/2/06)

Some special elements:Some special elements:

•• Explicit that a single SCRO may provide Explicit that a single SCRO may provide

guidance for more than one institutionguidance for more than one institution

•• SCROsSCROs require investigators to evaluate require investigators to evaluate

““probable pattern and effects of differentiation probable pattern and effects of differentiation

and integration of the human cells into the and integration of the human cells into the

nonhuman animal tissuesnonhuman animal tissues””

•• Provides medical insurance for Provides medical insurance for oocyteoocyte donors donors

in the event of donationin the event of donation--related complicationsrelated complications

Advisory Committee on Human Embryonic Stem Cell Advisory Committee on Human Embryonic Stem Cell

Research Research created by National Academies, 2006created by National Academies, 2006

2007 Amendments to Guidelines2007 Amendments to Guidelines

�� Clarification of Clarification of ““acceptably derivedacceptably derived””

when imported from another when imported from another

institutioninstitution

�� Institutions may share ESCRO Institutions may share ESCRO

committeescommittees

�� Reiterate sperm donor consent Reiterate sperm donor consent

requirementrequirement

Theorized alternative method 1Theorized alternative method 1LanzaLanza et al, et al, NatureNature 21 Oct 0521 Oct 05

Theorized alternative method 2Theorized alternative method 2MeissnerMeissner and and JaenischJaenisch, , NatureNature 21 Oct 0521 Oct 05

UNIVERSCITY OCF PENNSYLVANIA CENTER FOR ......California Proposition 71: “Stem Cell Research and...

Documents

Transcript of UNIVERSCITY OCF PENNSYLVANIA CENTER FOR ......California Proposition 71: “Stem Cell Research and...