based on

Testimony offered on S25, An Act Promoting

Stem Cell Research

Presented to the Joint Committee on Economic

Development and Emerging Technology

Marjorie Clay, PhD

UMass Medical School

Medical Ethicist

Wednesday, February 16, 2005

What are stem cells?

Cells that have the ability to divide for Cells that have the ability to divide for long periods of time.long periods of time.

Cells that are developmentally Cells that are developmentally “plastic”: they can take different “plastic”: they can take different pathways and develop different cell pathways and develop different cell types.types.

Types of stem cells

Totipotent Totipotent stem cells can give rise to a fully stem cells can give rise to a fully functional organism. . . .functional organism. . . .

. . . . AND to every cell type in the body.. . . . AND to every cell type in the body.

PluripotentPluripotent stem cells can give rise to virtually stem cells can give rise to virtually any tissue type. . . any tissue type. . .

. . . . but NOT to a fully functional organism.but NOT to a fully functional organism.

Levels of differentiation

In late 1998, James Thompson at UW-Madison discovered how to isolate and culture hES cells.

Sources of stem cells

Adult Stem Cells Adult Stem Cells Embryonic Stem CellsEmbryonic Stem Cells Embryonic Germ CellsEmbryonic Germ Cells Induced Pluripotent Stem CellsInduced Pluripotent Stem Cells

Adult Stem Cells

Haven’t been isolated for all tissue typesHaven’t been isolated for all tissue types

Present in small quantitiesPresent in small quantities Difficulties in isolation and purificationDifficulties in isolation and purification

Differentiate into a narrower range of Differentiate into a narrower range of cell typescell types

Numbers and quality decrease with ageNumbers and quality decrease with age

Induced Pluripotent Stem Cells (iPS)

•• iPS are a type of pluripotent stem cell iPS are a type of pluripotent stem cell artificially derived from a non-pluripotent artificially derived from a non-pluripotent cell, typically an adult somatic cell. cell, typically an adult somatic cell.

•• iPS were first produced in 2006 from iPS were first produced in 2006 from mouse cells and in 2007 from human cells. mouse cells and in 2007 from human cells.

•• iPS are not totipotent and do not involve iPS are not totipotent and do not involve the destruction of an embryo.the destruction of an embryo.

Shinya YamanakaJames Thomson

Induced Pluripotent Stem Cells (iPS)

•• Master regulator genes (turn other genes on Master regulator genes (turn other genes on or off)or off)

•• Oncogenes might be turned on. [Feb. 2008]Oncogenes might be turned on. [Feb. 2008]

•• Retroviruses can slip other genes into the Retroviruses can slip other genes into the chromosomes. chromosomes.

Sources of Embryonic Stem Cells

Embryonic stem cell linesEmbryonic stem cell lines

Therapeutic cloningTherapeutic cloning

Excess embryos from IVF clinicsExcess embryos from IVF clinics

Embryos created for research by IVFEmbryos created for research by IVF

Starting an embryonic stem cell line

We start with this. . .

. . .and end with this:

Ethical problem: derivation

Is it unethical to harvest stem cells?

Is it murder, as some opponents of stem cell research have argued?

““Thus the fruit of human generation, Thus the fruit of human generation, from the from the first moment of its existencefirst moment of its existence, that is to say , that is to say from the moment the zygote has formedfrom the moment the zygote has formed, , demands the unconditional respect that is demands the unconditional respect that is morally due to the human being in his bodily morally due to the human being in his bodily and spiritual totality.”and spiritual totality.”

““The human being is to be respected and The human being is to be respected and treated as a person treated as a person from the moment of from the moment of conceptionconception; and therefore ; and therefore from that same from that same momentmoment his rights as a person must be his rights as a person must be recognized, among which in the first place is recognized, among which in the first place is the inviolable right of every innocent human the inviolable right of every innocent human being to life.”being to life.”

Should we treat blastocysts as persons?

Congregation for the Doctrine of the Faith: Instruction on Respect Congregation for the Doctrine of the Faith: Instruction on Respect for Human Life in its Origin and on the Dignity of Procreationfor Human Life in its Origin and on the Dignity of Procreation

Some observations

The ethical theory used by some opponents of The ethical theory used by some opponents of stem cell research is called natural law theory.stem cell research is called natural law theory.

It is based on an Aristotelian view of It is based on an Aristotelian view of science, biology, etc.science, biology, etc.

Our knowledge of biology has changed a Our knowledge of biology has changed a great deal since Aristotle!great deal since Aristotle!

First, there is no “moment” of conceptionFirst, there is no “moment” of conception..

Reaching this two-cell stage takes about 30 hours total.

Reaching this morula stage takes about 40 hours total.

It takes about 24 hours to fertilize an egg.It takes about 24 hours to fertilize an egg.

None of these zygotes have the potential to become human beings because they are not implanted in a uterus.

Second, until implantation, no “embryo” exists.

Reaching the blastocyst stage takes between 5-6 days total.

Many complex changes must occur before implantation is complete (at about 13 days).

Ethical implications

There is no single ‘moment’ of conception.There is no single ‘moment’ of conception. Without a “host,” fertilized eggs neither are -- Without a “host,” fertilized eggs neither are --

nor can they become -- persons.nor can they become -- persons.

Because a blastocyst created for research Because a blastocyst created for research purposes will not be implanted in a uterus, it is purposes will not be implanted in a uterus, it is not a potential person.not a potential person.

A cell taken from a blastocyst before A cell taken from a blastocyst before implantation is not -- nor can it become -- a implantation is not -- nor can it become -- a person. [Taken from the inner cell mass and so person. [Taken from the inner cell mass and so is only pluripotent].is only pluripotent].

Should we treat blastocysts as persons?

Congregation for the Doctrine of the Faith: Instruction on Respect Congregation for the Doctrine of the Faith: Instruction on Respect for Human Life in its Origin and on the Dignity of Procreationfor Human Life in its Origin and on the Dignity of Procreation

““Thus the fruit of human generation, from the Thus the fruit of human generation, from the first moment of its existence, that is to say first moment of its existence, that is to say from the moment the zygote has formed, from the moment the zygote has formed, demands the unconditional respect that is demands the unconditional respect that is morally due to the human being in his bodily morally due to the human being in his bodily and spiritual totality.”and spiritual totality.”

Ethical implications

Not all fertilized eggs become implanted in a Not all fertilized eggs become implanted in a uterus; some are passed in menstruation. Does uterus; some are passed in menstruation. Does anyoneanyone treat these fertilized eggs as if they were treat these fertilized eggs as if they were persons?persons?

What would it mean to give them ‘the unconditional What would it mean to give them ‘the unconditional respect that is morally due to the human being in his respect that is morally due to the human being in his bodily and spiritual totality’?bodily and spiritual totality’?

Would we allow cryopreservation of zygotes if we Would we allow cryopreservation of zygotes if we thought they were living persons? thought they were living persons?

What follows from those observations?

We We don’tdon’t treat zygotes as human persons and treat zygotes as human persons and there are good scientific reasons why we don’t.there are good scientific reasons why we don’t.

Until implanted in a uterus, zygotes do not have the conditions necessary for development.

Nor do we have a moral obligation to provide those conditions.

If we did have an obligation, it would require “rescuing” fertilized eggs passed in menstruation.

Sources of Embryonic Stem Cells

Embryonic stem cell linesEmbryonic stem cell lines

Therapeutic cloningTherapeutic cloning

Excess embryos from IVF clinicsExcess embryos from IVF clinics

Embryos created for research by IVFEmbryos created for research by IVF

Does this “argument” make sense?

If we thought they were human persons, would we “pitch ‘em”?

400,000 fertilized eggs have been frozen and 400,000 fertilized eggs have been frozen and stored since the late 1970s.stored since the late 1970s. [American Society of Reproductive Medicine study][American Society of Reproductive Medicine study]

In July 2002, the DHHS designated $900,000± In July 2002, the DHHS designated $900,000± to support “embryo adoption.”to support “embryo adoption.”

Many ethicists oppose the use of this term because it is inaccurate and misleading:• a fertilized egg is not an embryo• misapplication of adoption law

• substitutes labels for argument.

Sources of Embryonic Stem Cells

Embryonic stem cell linesEmbryonic stem cell lines

Therapeutic cloningTherapeutic cloning

Excess embryos from IVF clinicsExcess embryos from IVF clinics

Embryos created for research by IVFEmbryos created for research by IVF

Somatic cell nuclear transfer

Remove DNA from egg cell; insert a body (somatic) cell.

Does therapeutic cloning start us down a slippery slope . . . .

. . . to reproductive cloning?

Source: “Stem Cells: A Primer”

90% of what we know about early human 90% of what we know about early human development is inferred from studies on development is inferred from studies on mouse embryos.mouse embryos.

Embryonic stem cells provide a window Embryonic stem cells provide a window into early human development that into early human development that researchers have never had before.researchers have never had before.

Developmental Research

Potential Clinical Uses

Identify teratogensIdentify teratogens Drug toxicity testsDrug toxicity tests

Regenerative medicineRegenerative medicine

Cardiomycetes for heart diseaseCardiomycetes for heart disease Islet cells for diabetesIslet cells for diabetes

Neural cellsNeural cells

ImmunodeficiencyImmunodeficiency

Juvenile DiabetesJuvenile Diabetes Multiple SclerosisMultiple Sclerosis Parkinson’s DiseaseParkinson’s Disease Alzheimer’s DiseaseAlzheimer’s Disease LeukemiaLeukemia ArthritisArthritis

Muscular DystrophyMuscular Dystrophy Lou Gehrig’s DiseaseLou Gehrig’s Disease Spinal InjuriesSpinal Injuries BurnsBurns Heart failureHeart failure StrokeStroke

The target diseases/conditions

The Benefits of Stem Cell Research

““We believe that not to develop the technology We believe that not to develop the technology would do great harm to over 100 million patients would do great harm to over 100 million patients in the United States alone who are affected by in the United States alone who are affected by diseases potentially treatable by the many diseases potentially treatable by the many medical applications of hES cells.” medical applications of hES cells.”

Thomas B. OkarmaThomas B. OkarmaGeron President and Chief Executive OfficerGeron President and Chief Executive Officer““Human Embryonic Stem Cells: A Primer on the Human Embryonic Stem Cells: A Primer on the Technology and Its Medical Applications”Technology and Its Medical Applications”

Drug Development and Testing

http://www.news.wisc.edu/9064.html

hES Cell-derived cardiac cells spontaneously organize themselves and begin to beat.

Tissue/Cells for Therapy MS results from a degradation of MS results from a degradation of

myelin, resulting in the myelin, resulting in the interruption of electrical signals interruption of electrical signals traveling down nerve fibers.traveling down nerve fibers.

Shiverer mice have an MS-like Shiverer mice have an MS-like condition, and so are used as a condition, and so are used as a model to study potential MS model to study potential MS treatments.treatments.

Researchers injected stem cells Researchers injected stem cells from a healthy mouse into the from a healthy mouse into the brains of shiverer mice. The stem brains of shiverer mice. The stem cells multiplied, migrated cells multiplied, migrated throughout the brain, and became throughout the brain, and became myelin-producing cells. Injected myelin-producing cells. Injected mice stopped shivering.mice stopped shivering.

If injected young enough, shiverer If injected young enough, shiverer mice never start shivering.mice never start shivering.

Impatient Patients

• Stem cells may be able to replace damaged cells in the body.

•• Today: lymphoma, leukemiaToday: lymphoma, leukemia

•• Future? Parkinson’s, Future? Parkinson’s, Alzheimer’s, diabetes...Alzheimer’s, diabetes...

The real ethical issues

The distinction between public and private The distinction between public and private sectors and the question of oversightsectors and the question of oversight

Creating a “level playing field”Creating a “level playing field”

Minimizing the occurrence of ‘mistakes’ Minimizing the occurrence of ‘mistakes’ and unintended consequencesand unintended consequences

Limiting applications and participantsLimiting applications and participants

(e.g., control misuses of power)(e.g., control misuses of power)

The real ethical issues (con’d)

Justice: access and distributionJustice: access and distribution

Questions raised by commercialization Questions raised by commercialization (e.g., patents, ownership, profit, (e.g., patents, ownership, profit, corporations, shareholders and other corporations, shareholders and other third-party sponsors)third-party sponsors)

In Georgia, 60% of urban white women age 40+ but only 0.5% of rural African-American women age 40+ used prenatal genetic testing.

Will using stem cells cause us to devalue

life?

Uniformly applied regulations should do much to prevent this outcome.

Conclusion Immanuel Kant -- “Ought implies can.”Immanuel Kant -- “Ought implies can.” ““Technological imperative” -- “Can Technological imperative” -- “Can

implies ought.”implies ought.” Ethical position -- “Not all that we Ethical position -- “Not all that we cancan

do but only what we do but only what we shouldshould do.” do.” All things considered, promoting stem cell All things considered, promoting stem cell

research is an ethically sound decision. It is research is an ethically sound decision. It is something we something we shouldshould do: we owe it to the do: we owe it to the 100+ million people who might be helped.100+ million people who might be helped.