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Testimony offered on S25, An Act Promoting Stem Cell Research Presented to the Joint Committee on Economic Development and Emerging Technology Wednesday, February 16, 2005

Marjorie Clay, PhD Medical Ethicist UMass Medical School

What are stem cells? ƒ

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

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

Types of stem cells Totipotent stem cells can give rise to a fully functional organism. . . . . . . . AND to every cell type in the body. Pluripotent stem cells can give rise to virtually any tissue type. . . . . . . but NOT to a fully functional organism.

Levels of differentiation

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

Sources of stem cells ƒ ƒ ƒ ƒ

Adult Stem Cells Embryonic Stem Cells Embryonic Germ Cells Induced Pluripotent Stem Cells

Adult Stem Cells ƒ Haven’t been isolated for all tissue types ƒ Present in small quantities ƒ Difficulties in isolation and purification ƒ Numbers and quality decrease with age ƒ Differentiate into a narrower range of cell types

Induced Pluripotent Stem Cells (iPS) • iPS are a type of pluripotent stem cell artificially derived from a nonpluripotent cell, typically an adult somatic cell. • iPS were first produced in 2006 from mouse cells and in 2007 from human cells. • iPS are not totipotent and do not involve the destruction of an embryo.

James Thomson

Shinya Yamanaka

Induced Pluripotent Stem Cells (iPS) • Master regulator genes (turn other genes on or off) • Oncogenes might be turned on. [Feb. 2008] • Retroviruses can slip other genes into the chromosomes.

Sources of Embryonic Stem Cells ƒ Embryonic stem cell lines ƒ Excess embryos from IVF clinics ƒ Embryos created for research by IVF ƒ Therapeutic cloning

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?

Should we treat blastocysts as persons? Congregation for the Doctrine of the Faith: Instruction on Respect for Human Life in its Origin and on the Dignity of Procreation

“The being is to begeneration, respected and “Thushuman the fruit of human from the treated as a person from the moment first moment of its existence, that is toofsay conception; and therefore from same from the moment the zygote hasthat formed, moment his as a person mustthat be is demands therights unconditional respect recognized, which in the first is morally dueamong to the human being in hisplace bodily the inviolable right of every innocent human and spiritual totality.” being to life.”

Some observations „

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

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

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

First, there is no “moment” of conception. It takes about 24 hours to fertilize an egg. Reaching this two-cell stage takes about 30 hours total. Reaching this morula stage takes about 40 hours total. 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 „ „

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There is no single ‘moment’ of conception. Without a “host,” fertilized eggs neither are -nor can they become -- persons. Because a blastocyst created for research purposes will not be implanted in a uterus, it is not a potential person. A cell taken from a blastocyst before implantation is not -- nor can it become -- a person. [Taken from the inner cell mass and so is only pluripotent].

Should we treat blastocysts as persons? Congregation for the Doctrine of the Faith: Instruction on Respect for Human Life in its Origin and on the Dignity of Procreation

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

Ethical implications „

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

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

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

What follows from those observations? „

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

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

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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 ƒ Embryonic stem cell lines ƒ Embryos created for research by IVF

ƒ Excess embryos from IVF clinics ƒ Therapeutic cloning

Does this “argument” make sense?

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

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

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

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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 ƒ Embryonic stem cell lines ƒ Excess embryos from IVF clinics ƒ Embryos created for research by IVF ƒ Therapeutic cloning

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”

Developmental Research 90% of what we know about early human development is inferred from studies on mouse embryos. Embryonic stem cells provide a window into early human development that researchers have never had before.

Potential Clinical Uses ƒ Identify teratogens ƒ Drug toxicity tests ƒ Regenerative medicine ƒ Cardiomycetes for heart disease ƒ Islet cells for diabetes ƒ Neural cells ƒ Immunodeficiency

The target diseases/conditions ƒ ƒ ƒ ƒ ƒ ƒ

Juvenile Diabetes Multiple Sclerosis Parkinson’s Disease Alzheimer’s Disease Leukemia Arthritis

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Muscular Dystrophy Lou Gehrig’s Disease Spinal Injuries Burns Heart failure Stroke

The Benefits of Stem Cell Research “We believe that not to develop the technology would do great harm to over 100 million patients in the United States alone who are affected by diseases potentially treatable by the many medical applications of hES cells.” Thomas B. Okarma Geron President and Chief Executive Officer “Human Embryonic Stem Cells: A Primer on the 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 myelin, resulting in the interruption of electrical signals traveling down nerve fibers.

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

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

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If injected young enough, shiverer mice never start shivering.

Impatient Patients • Stem cells may be able to replace damaged cells in the body. • Today: lymphoma, leukemia • Future? Parkinson’s, Alzheimer’s, diabetes...

The real ethical issues ƒ

The distinction between public and private sectors and the question of oversight  Creating a “level playing field”  Limiting applications and participants (e.g., control misuses of power) Minimizing the occurrence of ‘mistakes’ and unintended consequences

The real ethical issues (con’d) ƒ Questions raised by commercialization (e.g., patents, ownership, profit, corporations, shareholders and other third-party sponsors) ƒ Justice: access and distribution 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 „ „ „

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Immanuel Kant -- “Ought implies can.” “Technological imperative” -- “Can implies ought.” Ethical position -- “Not all that we can do but only what we should do.” All things considered, promoting stem cell research is an ethically sound decision. It is something we should do: we owe it to the 100+ million people who might be helped.