“What You Need to Know about Stem Cells” Presenter’s Notes Accompanying the PowerPoint Presentation

“Human Therapeutic Cloning SCNT” For a diagram that combines diagrams 2 and 3 above, see: "IVF and SCNT Stem Cell Sources" By clicking on these images try using a right-click, if your mo

“What You Need to Know about Stem Cells”

Presenter’s Notes Accompanying the PowerPoint Presentation

Prepared by the Stem Cell Action Network (SCAN)

www.stemcellaction.org The notes in this document amplify information in the SCAN PowerPoint presentation on stem cell research You can use these notes to help you give this presentation to an audience Additional materials that you may find helpful in preparing your presentation are available online at: http://www.stemcellaction.org/presentation.htm

The presentation and these notes are designed to serve the needs of a presenter who is not a scientist and who does not know much about stem cell research Please don’t be

intimidated by the complexity of this subject! Technical expertise is not needed to give this presentation.

These notes are posted on the SCAN website at

www.stemcellaction.org/presentation.htm Encourage those in your audience who have Internet access to read these notes if they wish to learn more about the points made in your presentation

Also helpful in “boning up” on the basics of SCR (stem cell research) are the following online resources:

Regarding the science of stem cell research:

Princeton University Department of Molecular Biology

http://www.molbio.princeton.edu/courses/mb427/2001/projects/09

Stem Cell Network (a Canadian organization)

http://www.stemcellnetwork.ca/engage

National Institutes of Health (NIH) Stem Cell Information

http://stemcells.nih.gov/index.asp

Regarding he ethics of stem cell research:

http://www.physweekly.com/archive/99/10_04_99/pc.html

Stem cell research is a many-faceted enterprise In preparing your presentation, don’t feel that you have to cover every single point made on the slides And don’t be daunted

by the amount of material that we’ve included in these notes We realize that this is much more information here than would ever be fitted into a talk on this subject

Tailor what you say to the needs and attention span of your audience Choose whatever you believe will be relevant and helpful to that audience If questions are thrown at you that you cannot answer, then relay them to us at SCAN (Idelle@stemcellaction.org), and

we will try to reply in a timely way

Here are addition guidelines

1 There are several ways of giving this presentation to an audience If you do not have access to PowerPoint presentation technology, then you may take a “low-tech” approach, using only printed materials Especially for an audience of ten or twenty or so, that will work fine

2 Whatever form your presentation takes, it’s a good idea to accompany your talk with a printed document that you hand out to members of your audience You can make copies of the Word-document version of the presentation at your local photocopy shop and distribute them to your audience (This document includes the two slides on California You may delete them if you're addressing a non-California audience.)

3 You can also ask the photocopy shop to make 11X17 inch color representations

of the three explanatory diagrams in the presentation:

1 "Embyronic Stem Cells”

2 “Stem Cells from In Vitro Fertilization (IVF)”

3 “Human Therapeutic Cloning (SCNT)”

For a diagram that combines diagrams 2 and 3 above, see: "IVF and SCNT Stem Cell Sources"

By clicking on these images (try using a right-click, if your mouse has one), you can download them to your computer You can then email them to your local photocopy shop, to be printed out

in 11X17-inch color Kinkos will do this for less than $2/slide If your audience is a small one, you can display the printed images to them while you discuss the scientific aspects of the

research

In June, we will hold the "First International Stem Cell Action Conference" at the

University of California in Berkeley Please invite your audience members to attend this historic event You can download, copy, and distribute the Conference Flier to your audience.

4 You can go to your local photocopy shop and ask them to make 11X17 inch color representations of the three explanatory diagrams in the presentation, entitled

 “Embyronic Stem Cells”

 “Stem Cells from In Vitro Fertilization”

 “Human Therapeutic Cloning (SCNT)”

For a diagram that combines the last two diagrams above, see: "IVF and SCNT Stem Cell Sources"

Files containing these images are posted at

http://www.stemcellaction.org/presentation.htm

By right-clicking on these images you can download them to your computer You can then email them to your local photocopy shop, and they can print them out in 11X17 color Kinkos will do this for less than $2/slide

It is a good idea to accompany your talk with a printed hand-out that you

distribute to members of your audience We have prepared such a hand-out and

it is available at: http://www.stemcellaction.org/presentation.htm

5 You presentation is an overview, and in most cases shouldn’t last longer than 30

to 45 minutes You don’t want to lose the interest and attention of your audience

6 The most important parts of your presentation are likely to be the science, ethics, and advocacy of the research You may wish to focus on these three areas, giving less attention to the details of the political regulation and support for the research

7 Be sure to hand out to your audience the flier about the conference, and invite audience members to attend Encourage members to learn more about the conference by visiting the website www.fisca.info, and/or telephoning Raymond Barglow, whose phone number is at the bottom of the flier (The conference flier

is included as Appendix 3 of this document, and is also available on line at http://www.stemcellaction.org/presentation.htm.)

8 Ask audience members to provide you with their email addresses, if they are willing to be added to the SCAN emailing list or if they have an interest in the conference

9 Encourage discussion during or following your presentation Be open to

questions that audience members ask about any aspect of the research – scientific, ethical, or political If people have qualms about the prospects or ethics of the research, they should feel free to express them Please remain tolerant and friendly toward people who question the research for one reason or another

Slide: What are stem cells?

Stem cells are the raw material from which all of the body’s mature, differentiated cells are made Stem cells give rise to brain cells, nerve cells, heart cells, pancreatic cells, etc

The cells that make up a human body are of different types and specialize in doing specific kinds of work, just as in society, different people have different jobs All cells, however, either are stem cells or come from stem cells Cells of the heart, the brain, bones, the pancreas – whatever kind of cell you care to mention – all have their origins

in the versatile stem cell

Once a stem cell has specialized, however, it cannot develop into yet another type of cell Stem cells don’t get to change careers cell differentiation is an irreversible process

Stem cells are found in embryos during their first few days of development, in fetal tissue, and more rarely in organs such as the heart, bones, brain, etc

Slide: What’s so special about stem cells?

 They are self-renewing they can replicate themselves over and over for a very long time

 They have the potential to replace cell tissue damaged by severe illnesses

 Understanding how stem cells develop into healthy and diseased cells will assist the search for cures

Stem cells are a raw material that has the capacity to renew itself Stem cells can divide over and over, for a very long time, generating an unlimited number of identical undifferentiated cells exactly like themselves A stem cell “line” is composed of a

culture of self-replicating stem cells

Stem cells generate all of the cell types that a human body needs Stem cells’ two

key properties – their self-renewing capacity and their capacity to become mature, specialized cells make them well suited to restoring tissue that has deteriorated Like

a very versatile building material, stem cells can be molded into just the right form to

repair a human body

Let’s look at this restorative process in a little greater detail, to better understand how

stem cell research can lead to cures Some children are born with organs that do not

work right A child with juvenile diabetes, for example, has a pancreas that does not generate enough insulin – a hormone needed by the body in order to digest sugars

Adults too sometimes have cells or entire organs that have become damaged so that they no longer function well In the brain of a person who has Parkinson’s or

Alzheimer’s disease, for example, neurons no longer work in the normal way In a spinal cord injury, crushed or damaged cells cause paralysis In a heart attack, heart

muscle is destroyed and replaced by useless scar tissue In each of these cases, the result is illness, disability, and suffering

Doctors and scientists have long been looking for a way to replace damaged or worn-out tissue in the human body with new healthy tissue, thereby giving patients a new lease of

life The most promising path to cures is the regeneration of differentiated tissue from stem cells, and especially from embryonic stem cells which are the most plastic

and versatile cells in the human body Research using these cells may yield the cures

needed by the nearly 100 million Americans afflicted by conditions ranging from

Parkinson’s, Alzheimer’s diseases, heart disease, and spinal cord injury to juvenile diabetes, multiple sclerosis, ALS, and many other medical conditions

It is, however, NOT only in the domain of regenerative medicine that stem cells will prove medically useful Here are two additional valuable applications of the research:

1 Scientists will observe and learn how stem cells give rise either to normal

differentiated cells or to diseased ones Discovering in this way how diseases begin and develop will help us find more effective treatments and cures

2 Stem cell research can also assist in the testing of drugs for safety and

effectiveness Before trying a new drug out on human subjects, we can see how

it affects the development of stem cells into healthy or diseased tissue

Slide: Two kinds of stem cells

 Embryonic (also called “pluripotent”) stem cells are capable of developing into all the cell types of the body

 Adult stem cells are less versatile and more difficult to identify, isolate, and purify

Scientists work with both embryonic and adult stem cells These two kinds of stem cell have quite different properties, and research using both is essential – the

research will advance most effectively if it “walks on two legs,” so to speak

We don’t yet know which kind of stem cell – embryonic or adult will prove to be most useful for medical purposes Studies done on both stem cell types are likely to play an essential role in finding new treatments and cures

Most scientists believe, however, that embryonic stem cells are the more promising

because they are “pluripotent,” meaning that they have the potential to differentiate into

tissue of any organ (brain, liver, heart, pancreas, etc.) of the human body Adult stem

cells, on the other hand, are, at best, "multipotent," meaning that they generate just a

few tissue types

Adult stem cells exist in small amounts throughout the body They are relatively rare, however, and less plastic (capable of transforming into diverse cell types) than are embryonic stem cells Adult stem cells taken from the skin only become skin, cartilage cells only become cartilage, etc An additional problem with adult stem cells is that they don’t replicate well in a lab – so it’s difficult to obtain enough of them to work with

Embryonic cells hold more promise than adult ones for two additional purposes that we’ve already mentioned: 1) understanding the origins and development of disease processes, and 2) testing new drugs

It should be noted, however, that to date, only adult stem cells have been used successfully in medical therapies – most notably in treatments for non-Hodgkin’s lymphoma and Leukemia Embryonic stem cells have been used successfully for

treatment purposes in animal studies, but have not yet been shown to be effective for human beings

Moreover, using adult stem cells in medical treatment may have one significant

advantage over embryonic stem cells – the adult cells may be less likely than embryonic ones to stimulate the growth of tumors This is a potential problem that regenerative medicine may need to address and solve

Research using embryonic stem cells hasn’t been around as long as research using the adult variety But the pluripotency of these cells – their capacity to generate all of the body’s cell types may make them especially useful in understanding and healing illnesses of tissue deterioration or loss

Slide: Embryonic Stem cells

Researchers extract them from a 5-7 days old blastocyst

They can divide to form more of their own kind, thereby creating a stem cell line

This research aims to induce these cells to regenerate tissue that the body needs

 Embryonic stem cells are found in a days-old embryo called a blastocyst A

blastocyst is a ball of between 128 and 256 cells that exists from about day 5 to day 7 following conception

 The ES cells in a blastocyst are part of the inner cell mass (ICM) These cells

are removed from the blastocyst and cultured – in a petri dish for example where they can be kept alive and encouraged to reproduce, thereby creating a stem cell line This procedure destroys the blastocyst

 ES cells are pluripotent - they have the ability to become any type of cell in the body (except for cells in the placenta or umbilical cord, which are generated out

of the cells surrounding the ICM

 The medical potential of stem cells has convinced many people to support stem cell research, including research that works with embryonic stem cells One of the most famous advocates of ES cell research is Michael J Fox He has Parkinson’s Disease, and is the founder of the Michael J Fox Foundation, an organization that supports Parkinson’s Disease research Of the $17 million donated so far, over $4 million has gone to ES cell research

 Another famous advocate of ES cell research is Christopher Reeve, the star of the Superman movie series When he was thrown from a horse, he severed his spine, losing the use of his arms and legs He regularly speaks on the

importance of ES cell research as a possible cure for his and other conditions

 Embryonic stem cell research is a very young science, and may have a long way

to go before it yields medical benefits It is noteworthy, though, that the curative potential of stem cells has already been demonstrated in animal studies Here are three examples:

1 Parkinson’s Disease A team led by Lorenz Studer, M.D at the Memorial

Sloan-Kettering Cancer Center, working with scientists from Cornell

University and the University of Connecticut, used cloned cells to generate dopamine nerve cells in mice – these are the cells that Parkinson's patients lack The cloning technique insured that these cells would be immunologically acceptable to these mice The mice had a disease very similar to Parkinson's, which the experimental therapy alleviated Possibly this kind of therapy can

be made to work with human beings as well

2 Juvenile Diabetes "Diabetes," the journal of the American Diabetes

Association (July 25, 2003), reports that researchers at the Univ of

Wisconsin observed mouse embryonic stem cells differentiate into a variety

of specialized cells, including insulin-producing cells Therapeutic cloning to generate such cells may solve problems facing promising therapies like the Edmonton protocol

The Edmonton protocol is a procedure developed in Canada for

transplanting healthy, insulin-producing islet cells into people with Type 1 diabetes Most Edmonton protocol treatments are quite successful –

experimental data indicate that the transplanted cells continue to generate insulin for years Two factors, however, limit the usefulness of this protocol: 1) Pancreatic islet cells are rare, and 2) the treatment induces a rejection response by the body’s immune system The second of these problems all but rules out the use of this treatment for children with juvenile diabetes Therapeutic cloning – as we will see in a moment could solve both of these problems

3 Spinal cord injury A number of studies done on animals with spinal cord

injuries have shown that stem cell transplants are capable of treating these injuries For example, a research team at the University of California at Irvine has demonstrated that when cells derived from human embryonic stem cells were transplanted into rats that had received a spinal cord injury,

improvements in the animals’ ambulatory activity could be observed

approximately one month later

Slide: Two Sources of Embryonic Stem Cells

1 Excess fertilized eggs from IVF (in vitro fertilization) clinics

2 Therapeutic cloning (somatic cell nuclear transfer)

There are currently two main sources of blastocysts – and of pluripotent stem cells derived from them that researchers can use to advance the search for cures:

1 Scientists can use stem cells from left-over embryos that would otherwise

be discarded from fertility clinics From these cells, healthy new tissue can

possibly be formed to replace the tissue that an illness or injury has damaged or destroyed

2 Scientists can use therapeutic cloning to generate stem cells for research

to find cures The technical term for therapeutic cloning is “somatic cell nuclear

transfer” (SCNT)

Slide: Stem Cells from In Vitro Fertilization (IVF)

 Excess embryos from IVF clinics In vitro fertilization is a method of assisted

reproduction “In vitro” means outside of the human body For couples who cannot have children in the usual way, in vitro fertilization unites an egg and a sperm in a laboratory setting This results in the formation of one or several

embryos (or “blastocysts,” more precisely), one of which can be implanted in a woman’s uterus, where it develops into a baby This procedure often leaves behind one or several excess embryos that are not implanted These embryos – which number in the hundreds of thousands in American fertilization clinics are frozen for future use or discarded They can also be used to contribute to the search for cures, since they are a potential source of embryonic stem cells

 Embryos created for research It would be possible to use in vitro fertilization –

with donated eggs and sperm to deliberately create blastocysts for research Stem cells extracted from these blastocysts would be used in experiments to advance scientific knowledge and the search for cures The blastocysts would be destroyed in the process of extracting their ES cells In England, the use of

embryos discarded by IVF clinics for stem-cell research is allowed, as is the

deliberate cloning of human embryos for this purpose

 The diagram shows 5 types of differentiated cells that pluripotent stem cells could generate: pancreatic, blood, heart, brain, and liver cells Of course this is not an exhaustive list Every kind of tissue in the human body could possibly be

regenerated from stem cells

Slide: Somatic Cell Nuclear Transfer (Therapeutic Cloning) Stem cells obtained

using this method originate not from a frozen embryo in an IVF clinic but from someone who has already been born The great advantage of stem cells generated in this way is that they could be implanted into the individual from whom they have been derived

without generating an immune response

The human body recognizes and attacks foreign cells, including stem cells A “foreign” cell is one that has different DNA (that is, different genetic material) than one’s own – as

is the case with the cells in an organ transplant, or a stem cell transplant when the stem cells come from someone other than the patient

The immune response is a serious obstacle to stem cell therapy – an obstacle that

therapeutic cloning eliminates SCNT, which begins with DNA taken from a patient’s cell, would produce stem cells that are genetically identical to that patient cell Therefore these stem cells, also containing the patient’s own DNA, could be used to treat the patient without encountering resistance from his or her immune system Just for this reason, SCNT-generated tissue solves problems that make donor tissue transplants difficult

Therapeutic cloning begins by taking a somatic (body) cell from an individual The nucleus of that somatic cell is fused with a donated egg that has had its nucleus

removed The resulting cell, with its new nucleus, is genetically identical to the individual because it contains the DNA from one of that individual’s somatic cells The new cell behaves like a fertilized egg and develops into a blastocyst ES cells are extracted from the blastocyst and grown in culture

This research cloning process, beginning with a person’s mature, differentiated cells and yielding stem cells genetically compatible with that person, was carried through

successfully by Korean scientist earlier this year The leader of the research team, Woo Suk Hwang says, "Our approach opens the door for the use of these specially developed cells in transplantation medicine.”

Notice that therapeutic cloning does not involve fertilization it does not involve the union of an egg and a sperm There is no “conception” and no creation of an “embryo” in the usual sense given to these words For this reason, even some people who believe

that a human person exists from the “moment of fertilization” approve of therapeutic cloning research, since it does not require fertilization at all

Most importantly, therapeutic cloning is not reproductive cloning This point

deserves emphasis, since many people aren’t away of crucial differences between these two kinds of cloning The blastocyst with which therapeutic cloning research works exists only in the laboratory It will never be implanted in a woman’s uterus to produce a baby Therapeutic cloning (SCNT) produces no cloned individual (as does reproductive cloning) but only cell tissue that can be used to heal an individual

Therapeutic cloning research is strongly approved by scientists This research is

endorsed by the American Medical Association, the National Academy of Sciences, the Association of American Universities, and many other medical, scientific, and

educational associations Almost all scientists who work in the domain of basic

biomedical research view therapeutic cloning (SCNT) research as crucial The National Academy of Sciences has concluded that therapeutic cloning "offers great promise for treating diseases closing these avenues of research may have real costs for millions

of people who now have these diseases."

Using embryonic cells derived from a person who has a genetically-based, we can examine the development and differentiation of those cells, and learn how the disease gets underway In their statement of support for therapeutic cloning research, forty Nobel Laureates say that it is needed not only to develop cell-replacement therapies, but also to increase our understanding of how inherited genetic predispositions lead to a wide variety of diseases A deeper understanding of how diseases arise will help us to cure them

Slide 12 The Ethical Debate.

In favor of ESCR:

Embryonic stem cell research (ESCR) fulfills the ethical obligation to alleviate human suffering Religious and secular ethical traditions recognize compassion as an essential ethical value We are called upon to help one another in times of need and suffering In the Christian tradition, this is expressed as “Love thy neighbor.” The good Samaritan in Jesus’ parable is applauded because he offers healing to the suffering stranger In Judaism, Islam, Buddhism, Hinduism and other religions, doing what we can to remedy human suffering is an ethical ideal

Since excess IVF embryos will be discarded anyway, isn’t it better that they be used in valuable research? Using an embryo in biomedical research to find cures is clearly ethically preferable to throwing it away It is worth noting as well that embryos didn’t first become “excessive” because of in-vitro fertilization In the course of nature itself, when

an egg is fertilized by a sperm inside a woman’s body, about half of the time this egg does not implant in the uterus That is, about one out of every two fertilized eggs is normally destroyed, without any outside human intervention whatever Is each of these fertilized eggs a person with an absolute right to life? What we confront here is the question: When does personhood really begin – a question that we will return to in a moment, and that these notes explore in detail in “Appendix 1 Following Conception, When Does Personhood Begin?”

SCNT (Therapeutic Cloning) produces cells in a petri dish, not a pregnancy

This is a point that we’ve already discussed Moreover, the distinction between

therapeutic and reproductive cloning can be made in legal terms For example, the

pro-research Hatch-Feinstein-Kennedy bill pending in the US Senate specifies that cloning

will serve only research purposes, and makes it illegal to implant a cloned egg into a

woman’s uterus

Against ESCR:

In SCNT, stem cells are taken from a days-old, human blastocyst, which is then

destroyed This amounts to “murder.” Given that we inhabit a world in which people do

treat one another inhumanely, and in which scientific research and technologies are

routinely used for destructive purposes – building bombs for example – we do to need to

take care that science serves only ethical purposes, and respects human life But can a

blastocyst really be counted as a person with a right to life? Does a blastocyst have an

inherent moral status that we should respect?

There are many individuals who believe that using human embryos – even if they are of

microscopic size and only a few days old – for any purpose other than achieving a

pregnancy is unethical This belief is grounded in the idea that the embryo is a

full-fledged person, with human interests and rights, from the earliest time of conception

There is a risk of commercial exploitation of the human participants in ESCR There exists the possibility that women could be mistreated and exploited in order to obtain eggs from them that will be used in this research This is an entirely legitimate concern But advocates of the research argue that our aim should be to regulate, not to criminalize, the procedures whereby scientists obtain egg cells for research purposes Moreover, there are clearly some cases where the

concern for improper incentives or risk of egg donation would not be relevant when a mother wishes to donate an egg to help her child, for example, or to create stem cells that could be used

to save her own life If a person can agree to participate, for example, in a dangerous malaria vaccine study to help prevent or cure this disease, why should she be prevented from donating eggs for similar (but much safer) lifesaving research?

Legislative bodies with the participation of scientists, medical practitioners, patients' groups, and other interested parties – may need to improve already existing statutes regarding egg donation for any purpose: in vitro fertilization, surrogate motherhood, or therapeutic cloning This is the democratic way to address the relevant social and ethical concerns

It is also important to note that by researching therapeutic cloning, scientists hope to understand

the biological properties of a cloned egg cell that induce it to generate stem cells Once

scientists learn how this cell “re-programming” occurs, they may no longer need to use egg cells at all.

For further discussion of questions about the donation eggs for research, see below:

“Appendix 2 Protecting Donors of Eggs for Medical Research”

Slippery slope argument: ESCR will lead to reproductive cloning A “slippery slope

argument” is an argument of the following form: A certain action should not be taken

because it is a stepping stone to another and another, until something terrible happens

Theoretically, therapeutic cloning could pave the way to reproductive cloning, because it

develops the technology and the knowledge that might make reproductive cloning

possible