Research: Status and Ethics

Richard Deem, Evidence for God from Science (www.GodAndScience.org)

Stem Cell Definition

A cell that has the ability to continuously divide and differentiate (develop) into various other kind(s) of cells/tissues

Introduction

Can we vs. should we

Dramatic advances of modern molecular genetics Should we ask the morality questions before attempting the can we questions?

Stem Cell/Cloning Topics

What are stem cells? History of stem cell/cloning research Possible uses of the technology Current status/knowledge Questions and known problems Legal considerations Politics Moral considerations

Kinds of Stem Cells

Stem cell type
Totipotent Totipotent

Description
Each cell can develop into a new individual

Examples
Cells from early (13 days) embryos

Pluripotent Cells can form any (over Some cells of blastocyst (5 to 14 Pluripotent 200) cell types days) Multipotent Cells differentiated, but Fetal tissue, cord Multipotent can form a number of blood, and adult other tissues stem cells

Stages of Embryogenesis
Day 2 2-cell embryo

Day 1 Fertilized egg

Day 3-4 Multi-cell embryo

Day 11-14 Tissue Differentiation

Day 5-6 Blastocyst

Derivation and Use of Embryonic Stem Cell Lines inner cell mass Isolate

Outer cells (destroys embryo) (forms placenta) Inner cells (forms fetus) Culture cells

Day 5-6 Blastocyst Liver Kidney

Special sauce (largely unknown) Heart repaired

Heart muscle

History of Stem Cell/Cloning Research

Who invented cloning and when? Stem cell research a new field of study? History of human stem cell research History of embryonic cell research History of cloning/human cloning

History of Human Stem Cell Research

In 1968, the first bone marrow transplant was successfully used in treatment of SCID Since the 1970s, bone marrow transplants have been used for treatment of immunodeficiencies and leukemias

Bone Marrow Stem Cells

History of Human Embryonic Cell Research

1954 John Enders received a Nobel prize in Medicine for growing polio virus in human embryonic kidney cells

History of Human Embryonic Stem Cell Research

In 1998, James Thomson (University of Wisconsin-Madison) isolated cells from the inner cell mass of the early embryo, and developed the first human embryonic stem cell lines. In 1998, John Gearhart (Johns Hopkins University) derived human embryonic germ cells from cells in fetal gonadal tissue (primordial germ cells). Pluripotent stem cell lines were developed from both sources

History of Somatic Cell Nuclear Transfer (Cloning)

1952 Briggs and King cloned tadpoles 1996 The first mammal cloned from adult cells was Dolly, the sheep. 1998 Mice cloned 1998 Cows cloned 2000 Pigs cloned

History of Cloning

CC Carbon Copy

2001 Cat cloned 2002 Rabbits cloned 2003 Mule cloned 2004 Bull serial-cloned 2005 Dog cloned

Possible Uses of Stem Cell Technology

Replaceable tissues/organs Repair of defective cell types Delivery of genetic therapies Delivery chemotherapeutic agents

Early Successes Adult Stem Cells

Human mesenchymal stem cells turned on genes found in bone, cartilage, adipose, muscle, hematopoiesis-supporting stromal, endothelial, and neuronal cells. Multipotent adult progenitor cells have been shown to differentiate into functional, hepatocyte-like cells.

Early Successes Adult Stem Cells

Human neural stem cells can migrate extensively in the brain after injection. Adult stem cells have been isolated from amniotic fluid, peripheral blood, umbilical cord blood, umbilical cord, brain tissue, muscle, liver, pancreas, cornea, salivary gland, skin, tendon, heart, cartilage, thymus, dental pulp, and adipose tissue.

Early Successes Human Cloning

2001 First cloned human embryos (only to six cell stage) created by Advanced Cell Technology (USA) 2004* Claim of first human cloned blastocyst created and a cell line established (Korea) later proved to be fraudulent
*Hwang, W.S., et al. 2004. Evidence of a Pluripotent Human Embryonic Stem Cell Line Derived from a Cloned Blastocyst. Science 303: 1669-1674.

Cloned Human ESC Differentiate Into Different Tissue Types Neural Retinal

Bone

Cartilage

Epithelial

Cloned Embryonic Stem Cells Advantages/Problem s Advantages

No rejection Prefect match Only 10% of cloned oocytes became embryos 0% (0 out of 2061) survived to become a cell line Genetic donor was same as egg donor (i.e., wont work for males!) Cost is high (health insurance probably won't pay)

Problems

Unknowns in Stem Cell/Cloning Research

It is uncertain that human embryonic stem cells in vitro can give rise to all the different cell types of the adult body. It is unknown if stem cells cultured in vitro (apart from the embryo) will function as the cells do when they are part of the developing embryo

Challenges to Stem Cell/Cloning Research

Stem cells need to be differentiated to the appropriate cell type(s) before they can be used clinically.

Recently, abnormalities in chromosome number and structure were found in three human ESC lines.

Challenges to Stem Cell/Cloning Research

Stem cell development or proliferation must be controlled once placed into patients.

Possibility of rejection of stem cell transplants as foreign tissues is very high.

Challenges to Stem Cell/Cloning Research

Contamination by viruses, bacteria, fungi, and Mycoplasma possible. The use of mouse feeder cells to grow ESC could result in problems due to xenotransplantation (complicating FDA requirements for clinical use).

Legal Considerations: Embryonic Cell Research 1973 moratorium on government

financing for human embryo research

1988 NIH Panel voted 19-2 in favor of government funding 1989 DHHS Secretary Sullivan extended the moratorium

Legal Considerations: Embryonic Cell Research voted to override 1990 Congress

the moratorium, vetoed by President Bush

1993 President Clinton lifted the ban 1994 the Human Embryo Research Panel favored research, but Clinton overrode the panel 1995 Congress banned federal funding

Legal Considerations: Embryonic Cell Research President Clinton August 25, 2000,

allowed funding of research based on cells from (aborted) human fetal lines, but not embryonic cells On August 9, 2001, President Bush announced his decision to allow Federal funds to be used only for research on existing human embryonic stem cell lines created prior to his announcement

Right to Life
The Declaration of Independence of the United States guarantees certain unalienable Rights, that among those are Life, Liberty and the pursuit of Happiness

Laws Banning Reproductive Cloning (as of 2004)

Laws Banning Research Cloning (as of 2004)

Worldwide Stem Cell Regulations

2003 proposal to ban reproductive and research cloning worldwide was tabled by the United Nations following objections by Great Britain and other countries The proposal will be taken up again in 2004, but dropped

Embryonic Reproductive Cloning Laws Worldwide

Embryonic Research Cloning Laws Worldwide

Stem Cells and Politics

The California Stem Cell Research and Cures Initiative Nancy Reagan Michael Reagan Congress John Kerry

The California Stem Cell Research and Cures Initiative

November, 2004 ballot initiative

Established the California Institute for Regenerative Medicine Run by an Independent Citizen's Oversight Committee composed of politicians, advocacy groups, and executive officers of universities Indebted the state of California for $3,000,000,000 in State General Obligation Bonds

The California Stem Cell Research and Cures Initiative

ICOC requires grantees to purchase goods and services from California suppliers (> 50%) Established real estate development and facilities construction for research (up to 10% of total funding) 3% for general administration, 3% for grant administration Up to $6,000,000 per grantee/year

The California Stem Cell Research and Cures Initiative

Although the initiative purported to fund all manner of stem cell research, a clause prevents funding of any stem cell research other than embryonic stem cell research: other research categories funded by the National Institute of Health shall not be funded by the Institute

Passed by voters, November, 2004

Nancy Reagan and Embryonic Stem Cell Research

Nancy Reagan pushing embryonic stem cell research as cure for Alzheimer's disease. Alzheimer's disease is due to pathology that spreads from affected cells to healthy cells Stem cell treatments, if they worked, would also become abnormal shortly after treatment

Michael Reagan: My Father Opposed Embryo Destruction

my father, as I do, opposed the creation of human embryos for the sole purpose of using their stem cells as possible medical cures. Called media references to ESC cures as junk science. Quoted ESC researchers who say that ESC are unlikely to cure Alzheimers Disease

Congress Calls for Review of White House ESC Policy

206 representatives said that the current policy, instituted by Bush in August 2001, have slowed potentially lifesaving research (4/30/04) 58 Senators (including 14 Republicans) called for President Bush to reverse his ESC policy (6/4/04)

John Kerry Says Bush Has politicized science

While the Bush administration has politicized science, Kerry will put America back on the path of scientific excellence with a commitment to scientific research based on fact not ideology.

Moral and Ethical Considerations of Stem Cell and Cloning Research stem cells Adult

Embryonic stem cells

Embryo must be destroyed When does human life/personhood begin? Embryos (see above) Reproductive cloning

Human cloning

When Does Human Life Begin? Medical Embryology Textbooks Human: Clinically The Developing
Oriented Embryology Zygote: this cell results from the union of an oocyte and a sperm. A zygote is the beginning of a new human being (i.e., an embryo). Human development begins at fertilization This highly specialized, totipotent cell marks the beginning of each of us as a unique individual.

When Does Human Life Begin? Medical Embryology Textbooksof Human Embryology Essentials
In this text, we begin our description of the developing human with the formation and differentiation of the male and female sex cells or gametes, which will unite at fertilization to initiate the embryonic development of a new individual.

When Does Human Life Begin? Medical Embryology Textbooks

Human Embryology & Teratology Fertilization is an important landmark because, under ordinary circumstances, a new, genetically distinct human organism is thereby formed

When Does Human Life Begin? What Do Medical Doctors Say?

Dr. Alfred Bongioanni (University of Pennsylvania): I have learned from my earliest medical education that human life begins at the time of conception.

Dr. Jerome LeJeune (University of Descartes): after fertilization has taken place a new human being has come into being.

When Does Human Life Begin? What Do Medical Doctors Say?

Dr. Hymie Gordon (Mayo Clinic):

By all criteria of modern molecular biology, life is present from the moment of conception.

Dr. Micheline Matthews-Roth (Harvard University Medical School): It is scientifically correct to say that an individual human life begins at conception

Embryo Is Not a Person

Persons . . . are members of a social community that shapes and values them, and personhood must be defined in terms of interactions and relationships with others. Susan Sherwin. 1999. Ethical Issues: Perspectives for Canadians. Ed. Soifer, Eldon. Peterborough, Ontario: Broadview Press, p. 267

Embryo Is Not a Person Rebuttal

Personality definition problems

Does a human non-person exist? What traits define personhood? Who makes the definition? Society has excluded certain humans from personhood before (e.g., African slaves, Chinese, etc.) Should we make a new list of human non-persons?

Embryo Is Not a Person Rebuttal

The lack of certain personality traits would remove from personhood:

Those who are in a coma Elderly with degenerative disorders (Alzheimer's, etc.) Mentally deficient

Genetic Neurological disease Mental illness

Is is okay to consider these human beings as non-persons?

Definition of Personhood

One who is consciously performing personal acts

eliminates those who are sleeping

One with a present capacity to perform personal acts

eliminates those who are in a coma

Definition of Personhood

One who has a history of performing personal acts

eliminates one who was in a coma from birth, but wakes up

One with a future capacity for performing personal acts

makes those who are dying as nonpersons

Implications of Functionally-Defined Personhood

Newborns lack the ability to perform personal functions in fact, newborn humans are less capable physically and mentally than virtually all other mammals

Therefore, on the basis of functionally-defined personhood, newborns fail the test could be killed on the basis of nonpersonhood

At Conception, It Is Only a Single Cell

Claim:

Fertilized eggs are single cells, like blood cells or other parts of the body This single cell is unique from both the fathers and mothers cells and is the beginning of every new human being

Rebuttal:

Only a Small Percentage of Embryos Implant

Claim:

Embryos are only potential life. Most do not result in births 25-33% of women become pregnant in the first month 33% of implanted embryos die before birth There are countries in which over 25% of children die before age 5. Should we allow killing of children?

Rebuttal:

Frozen Embryos Are Going to Be Discarded Anyway

Proponents of human embryonic stem cell research say that embryos from IVF are going to be discarded and, so, should be used for research Prisoners on death row are also going to die, so why not do research on them?

Devaluation of Human Life

Right now it is only 5-12 day embryos When science discovers it is impossible to produce organs/tissues in the absence of surrounding developmental processes, scientists will demand the tissues be allowed to mature prior to harvest

Christian Arguments and Response

We may not do evil so that good will result (Romans 3:8) Humans are created in the image of God before birth The human soul begins before birth

Bible: Human Life Begins Before Birth

"Did not He who made me in the womb make him, And the same one fashion us in the womb? (Job 31:15) Yet Thou art He who didst bring me forth from the womb Thou hast been my God from my mother's womb. (Psalms 22:910) For Thou didst form my inward parts; Thou didst weave me in my mother's womb. I will give thanks to Thee, for I am fearfully and wonderfully made (Psalms 139:13-16) See also Isaiah 44:2, 24

When Does Ensoulment Occur?

John the Baptist: "For he will be great in the sight of the Lord, and he will drink no wine or liquor; and he will be filled with the Holy Spirit, while yet in his mother's womb." (Luke 1:15) Paul: But when He who had set me apart, even from my mother's womb, and called me through His grace (Galatians 1:15) Jeremiah: "Before I formed you in the womb I knew you, And before you were born I consecrated you; I have appointed you a prophet to the nations." (Jeremiah 1:5)

Murder Defined by the Bible

People are not to be murdered because they are created in the image of God. (Genesis 9:6) Murder must be intentional, with premeditation (Joshua 20:3) Killing of embryos is intentional, and premeditated

Biblical Arguments: Summary

The Bible indicates that God recognizes human beings as persons prior to development in the womb Bible defines murder as being intentional and premeditated ESC research destroys embryos that are considered as ensouled human beings

Morality of Human Reproductive Cloning

Be fruitful and multiply assumed to be natural, but IVF and cloning not mentioned in the Bible Problems with cloned animals most suffer premature aging and other genetic problems. Might be avoidable with better techniques? Biblical basis to condemn human reproductive cloning?