The Benefits of Pluripotent Stem Cell Research

                    Behnoud Taghavi-Farahi

                             English 102

                                  1422

                       Feburary 22, 2002

I. Human pluripotent stem cells

    A. Deriving process

    B.  Potential benefits

II. Possible cures

     A.  Alzheimer's

     B.  Parkinson's

     C.  Heart disease

     D.  Cancer

Ill.  Adult stem cells

      A. Bone marrow

      B. Non-rejecting

      C. Pluripotentency unnecessary

IV.  Adult stem cell drawbacks

       A. Isolating cells

       B. Lacking quantity / time / normality

       C. Advantages of ES cells

V. Umbilical Cord

      A. Extracting

      B. Drawbacks

VI. Parthenogenesis

      A. Extracting

      B. Parthnotes

      C. Drawbacks

VII. Rejuvenating Brain Cells

        A. Extracting

        B. Potential

        C. Drawbacks

VIII. Future Possibilities

        A. Understanding human cells

        B. Testing Medicine

        C. Reversing the aging process
 

         In 1998, scientists from two universities, Wisconsin and John Hopkins, were the first to

grow stem cells in laboratories.  A few years later they had discovered a method by which

to develop these stem cells into 110 types of human cells; the human body contains 220 types.

This procedure was revolutionary because it provided the necessary knowledge needed to
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further understand the human body.  " 'What makes stem cells special is that they are immortal,

and they can become anything they want to be,' " grants Dr. James Thomson of the University

of Wisconsin  (qtd. in Joseph  1). The introductions of antibiotics and vaccines, for example,

have dramatically improved the heath and well being of people, and now with this new discovery

the potentials are endless.  Recently, a panel established by the National Academy of Sciences,

led by Dr. Vogelstein, a professor of oncology and pathology at Johns Hopkins University, testified

in the Senate regarding the benefits of stem cell research.  Dr. Vogelstein and his panel, which

included scientists and researchers from Harvard School of Public Health, Columbia University,
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and Georgetown University, just to name a few, concluded that "Studies with human stem cells
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are essential [. . .] to make progress in the development of treatment for human disease"

(Stolberg).  Although opponents of stem cell research believe that there are other <<Thesis

avenues to treat patients with illnesses that donít involve the use of stem cells, the truth

is that the research on stem cells will provide the information needed to cure some of our

deadliest disorders, such as Alzheimer's, Parkinson's, heart disease, and others,

like cancer, allowing many individuals a chance to lead fulfillling lives.

         Embryonic stem cells, or human pluripotent stem cells, are mostly derived from fertility

clinics.  According to the Ontario Consultant on Religious Tolerance, embryos possess "two <direct

extremely valuable properties:  They can divide for long periods of time in the lab to produce
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more stem cells, [and] they can transform themselves into any of the cells present in the

human body" (Robinson  6).  In-vitro fertilization (in a petri dish) is used to extract the stem

cells from the embryo.  There are two forms of human pluripotent stem cell lines that have

produced the same result. The first, embryonic stem cells, was conducted by Dr. Thomson,

who was able to isolate pluripotent stem cells during the blastocyst stage by removing the

inner cell mass. The second method, embryonic germ cells, was achieved when Dr. John

Gearhart of Johns Hopkins University was able to isolate pluripotent stem cells from fetal

tissue after a patient, voluntarily, chose to end her pregnancy. There is also another form of

deriving stem cell lines, known as somatic cell nuclear transfer (SCNT), which the National

Institute of Health (NIH) explains as ìthe transfer of a nucleus from a somatic cell into <<direct

an egg from which the nucleus has been removed" ( 1 ).  This process involves taking an egg

and removing the nucleus, which contains the chromosomes.  The egg is then left with the

proteins, energy, and other nutrients that help it in the production of an embryo.  Finally,

using precise calculations and laboratory work, a somatic cell nucleus is fused with the

egg cell that had its nucleus removed.  The end result will allow the extraction of human

pluripotent stem cells during the blastocyst stage.  What does all of this have to do with

the average citizen?  The truth is that this new advancement in medical science will allow

the medical community to develop what is known as therapeutic cloning.  This revolutionary

procedure, which is still in its infancy, will greatly benefit everyone who suffers from any sort

of debilitating disease.  It will allow scientists to specialize pluripotent stem cells so they can

treat disabilities such as Alzheimerís, Parkinsonís, heart disease, and some cancers.

        There has been tremendous progress made with laboratory animals that puts researchers

one step closer in their pursuit for cures and the understanding of the fundamental structure of

being human.  Many of our diseases are attributed to the nervous systems, and since damaged

nerve cells cannot be replaced, no new source of functioning nerve tissue exists, and no therapeutic

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possibilities exist.  For example, In Alzheimerís disease, cells that are responsible for the

production of certain neurotransmitters die.  In Parkinson's disease, nerve cells that make

dopamine also die.  In both cases the nervous system does not have the capacity to rebuild

itself.  Despite the lack of cooperation by the nervous system, scientists have been able to
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inject stem cells into the brains of mice, and observe the cells ìreplac[ing] the dead tissue" <<direct
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and tak[ing] "over the functions of the old cells" (Joseph  2). Recently, at the Harvard University

Medical School, scientists were able to correct the symptoms of Parkinsonís in rats by injecting

embryonic stem cells into their brains, which in turn "became cells that make the chemical <<direct

dopamine" (Lerner  3).  Similar tests occurred at the National Institute of Neurological

Disorder and Stroke (NINDS), where Dr. Ronald McKay and his colleagues treated a disease

similar to Parkinson's in rats by taking stem cells from a rat's embryo.  The results were

promising: as Dr. McKay  insists, " 'about a 75% improvement in motor function 80 days <<qwq

 after they received the transplants' " (qtd. in Robinson  7).  The experiments conducted by

 these institutions show the promise that awaits us in the future.  The nervous system is

not the only beneficiary of human pluripotent stem cells;  the transplantation of healthy

heart muscle cells into an ailing heart is also feasible. "We plan on using these cells to<<direct

grow  heart tissue that  could replace diseased or dying heart muscle [. . .]," claims Dr. Thomson

(Joseph  2).  Researchers are hopeful that they can inject human pluripotent stem cells

into the heart, which will repopulate the heart tissue and work with the host cells in

order to make the heart function normally.  An experiment of this nature was performed by

Dr. Gearhart, who was able to coax stem cells into heart muscle cells and implant them into mice,
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while observing them "successfully repopulate the heart tissue and integrate with the host cells"

( Robinson  6).  Stem cells also play another role in the treatment of heart disease, according
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to scientists at New York Medical College in Valhalla: "[S]tem cells in the heart were able to <<direct

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regenerate cardiac muscle after a heart attack or other [injuries]"  (Lerner  3).  Besides heart

disease and the nervous system, cancers could also benefit from stem cell research.  Currently

bone marrow stem cells, from adult stem cells, are used to help treat patients who are exposed

to high levels of chemotherapy.  Unfortunately, adult stem cells have their limitations and canít
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"restore immune function completely." Scientists hope to inject manipulated stem cells into a patient

who is having a bone marrow transplant procedure. This will allow ìthe complete repertoire of [the]

immune response  to be restored  (AAAS  6).  According to the American Association for the

Advancement of Science and Institute for Civil Society, "Complete and functional restoration will
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be required if [. . .] immune/vaccine anticancer therapy is to work [. . .] [which] would permit [the]

use of very toxic (and effective) chemotherapeutic regimens that could not currently

be utilized [. . .]" ( 6 ).

        Despite the capabilities of pluripotent stem cells, opponents still argue about whether we

should use this process at all.  They mention the most talked about, non-embryonic stem cell,

which is the adult stem cell.  Adult stem cells are currently being used in bone marrow transplants.

The stem cells taken from adults provide red blood cells, white blood cells, and platelets, which are

an important factor in bone marrow transplantation.  There are advantages in using adult stem

cells over pluripotent stem cells, one being that they are not rejected by the body.  According to

David Prentice, who is a professor of life sciences at Indiana State University and an adjunct
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professor of medical & molecular genetics at the Indiana University School of Medicine, the "[use]

of human embryonic stem cells will require lifelong use of drugs to prevent rejection of the tissue."

If the stem cell is not properly manipulated, and is " 'injected into the body, [embryonic] stem cells

can produce tumors' " (qtd.  inLopez  4).  Other discoveries have been made which were thought to

Research published a study demonstrating that stem cells taken from adult bone marrow
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had been transformed into nerve cells" (OíMathuna  2).  Another study was demonstrated

during  the 43rd Annual Meeting of the American Society of Hematology (ASH),

when Dr. Donald Orlic and his colleagues from the National Human Genome Institute (NIH),

and New York Medical College  revealed that through laboratory testing they had been

successful in curing a diseased mouse heart by injecting bone marrow stem cells into the mouse ( 1 ).
paraphrase
In his studies, Dr. Orlic found that 73 percent of the treated animals survived, while only

17 percent of the non-treated  ones did  (ASH  1).  Anti-embryonic stem cell groups believe,

among other things, that the study of pluripotent stem cells is unnecessary since adult stem

cells have already been used clinically.  They argue that as research on this topic progresses adult

stem cells will help find all of the 220 known cell types in the human body.

         In order to respond to the opponents of pluripotent stem cells, we must first counteract

their misunderstanding of stem cells, and then guide them through their insufficient knowledge

of the limitations that adult stem cells possess.  The scientific community refers to human embryonic

stem cells as pluripotent, which means that they have the capacity to give rise to virtually any tissue

type, but not to a functioning organism like totipotents.  In contrast, adult stem cells are multipotent

stem cells, meaning that they could only give rise to a limited number of tissues.  To explain it in a

different manner, one must imagine a skyscraper:  The blueprints to it represent totipotent, the

foundation represents pluripotent, and the 50th floor and up represents multipotent, hence

the limitations.  The critics mention the usability of adult stem cells in which bone marrow had

been used for treatment.  Bone marrow transplantations are actually transplantations of hematopoietic

stem cells, which give rise to different blood cells.  Through pluripotent stem cells it will be possible

to culture a greater number of hematopoietic stem cells then those of which adult stem cells

are capable. Furthermore, any pluripotent stem cell can be multiplied far more easily than that
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of its competitor, adult stem cells.  "[B]ecause of the proliferative power of embryonic cells, they

will likely be used to produce large numbers of cells for use in clinical medicine," concedes

Dr. McKay  (Kent  55).  Adult stem cells have not been isolated for all tissue types.  They are
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present throughout the body, but only in minimal form, which makes them difficult to "isolate

and purify" (NIH  5).  Regarding the tissue rejection that may occur in embryonic stem cells,

the SCNT, explained earlier, would serve to prevent this from happening.  For example, since

SCNT inserts a patientís own DNA into an egg, the cloned embryo will contain the same genetic
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materials as the patient, hence the stem cell would not be rejected.  This would eliminate the

dangerous side effects and need for toxic drugs required in transplantation today.  If a patient

is in need of treatment, a stem cell from his own body would first have to be isolated then grown

in culture in substantial amounts before it is of any use to the patient (NIH  5).  If the stem cell is

vitally needed, there may not be adequate time to grow the cells for the patient.  Some patients

may have a genetic defect that would also be present in their stem cells, rendering it useless
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( 5 ).  "[S]tem cells from adults may not have the same capacity to proliferate as younger cells
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[. . .] ," noted the NIH. "[A]dult stem cells may contain more DNA abnormalities, caused by exposure
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to daily living, including sunlight [. . .] and by expected errors made in DNA replication during the

course of [oneís] life"  ( 5 ).  There are also many advantages to pluripotent stem cells.  For

example, according to Dr. Michael West, who is the president and CEO of Advanced Cell
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Technology (ACT), when SCNT occurs it "act[s] as [a] 'time machine' by taking the patient's <<qwq

cell back to an embryonic state" (qtd. in Fahy, Kent  40).  Other advantages could be to create stem

cells that "provide resistance to chemo- and radiation therapy, enhance immune response to direct

tumors, and induce tolerance to the transplantation of tissues and organs from other species"

(Kent  55).  David Baltimore, a Nobel laureate and researcher at Massachusetts Institute of

Technologyís Center for Cancer Research, said it most eloquently:

       display quotation  (no quote marks used, unless in original)
It has been suggested that adult tissues might provide an alternative source

of stem cells.  This is simply false. Adult tissues are not known to have cells

with the  potential to become all parts of the body.  In adults, certain

 tissues (e.g. skin, blood, and brain) do contain specialized types of

 stem cells, but they are not generic stem cells with the same properties

 as those derived from embryos. (qtd. in Kent  55) period placed inside

available for extracting non-embryonic stem cells.  Through this technique, a small amount of

blood is taken from an umbilical cord, which is rich in stem cells, that has been detached from

a newborn.  Similar to adult stem cells, the stem cells taken from the umbilical cord will be used
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to treat patients who are undergoing bone marrow transplants. "[C]ord blood [is] already <<direct

successfully being used clinically, while clinical use of embryonic stem cells is years away,"
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alleges Professor Prentice  (Lopez  4).  This may be true as trial applications of  embryonic

stem cells or embryonic germ cells are at least five to ten years away, according to Dr. Gearhart,

who is one of the original pioneers of pluripotent stem cell research (Joseph  3).  Professor

Prentice's argument does not hold merit because the use of  umbilical cord blood for bone

marrow transplants or any other procedure would fall under the same limitations as adult

stem cells.  Even though trial applications of stem cells are many years away, the benefits

that await us will make up for the lost time.  The amount of stem cells produced, which are

then manipulated for bone marrow transplants, will overshadow the number of umbilical cord

stem cells.  Umbilical cords and adult stem cells are good sources for treatment to be used as

part of the supporting cast of pluripotent stem cells -- not as a replacement for it.

         One fairly new advancement in non-embryonic stem cell research is known as Parthenogenisis,
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which is a Greek word meaning virgin birth.  In this procedure an egg cell can be activated and

made into an embryo, where the stem cell is extracted without the assistance of  sperm or new

DNA.  These new embryos are known to scientists as parthenotesand cannot develop into an

organism even if they are implanted in a womb  (Pollack).  Also, stem cells derived from the donorís

embryo would be genetically theirs.  Virtually any woman can have her egg turned into a parthenote

and benefit from the tissues produced especially for them.  This procedure would also eliminate
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the fear of  tissue rejection, since the egg belongs to the original donor.  This experiment has not

yet been successful in developing stem cells for humans, insists the ACT, but parthenotes have

been created and stem cells have been extracted from monkeys  (Pollack).  Every non-embryonic

stem cell covered so far has had drawbacks, and parthenogenisis is no exception.  For starters,

the embryo created excluded the Y chromosome, which may cause the embryo to "develop <<direct

incorrectly and produce abnormal tissue" (Pollack).  Additionally, this process will not work for

the female counterparts, which will make half of the population quite angry.

         A final method of extracting stem cells, through a non-embryonic process, falls under one

of the most complicated fields of study in medicine, the brain.  Scientists have been studying the

brain in hopes of discovering methods by which to replenish the damaged cells.  The region that

most are concentrating on is called the hippocampus area, which appears to contain a significant

number of stem cells.  Besides the notion of stem cells in the hippocampus area, scientists are

interested in rejuvenating this area of the brain because it manages memory, learning, and motor

skills.  One of the top researchers in brain rejuvenation is Dr. Helen Scharfman, who is a neurologist

at Helen Hayes Hospital in West Haverstraw.  " 'Our dream is to help the brain heal itself,' " she
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concurs.  The problem, however, is " ' How can we make [the cells] go to the right place? [and] [. . .]

[h]ow can we manipulate them to the body's advantage?' " (qtd. in Lerner 1-3).  Dr.  Scharfman
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will use the brains of rats and portions of human brains to try and find the answer.  "This is the

first glimmer of hope that we can modify the effects of a stroke, weeks, months, years after it

occurred," defends Dr. Lawrence R. Wechsler, who is a neurologist and director of the Stroke
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Institute at the University of Pittsburgh  (3).  There are drawbacks, however, to
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this type of research.  The NIH explains that "brain cells from adults that may be neuronal stem

cells [which help rejuvenate the brain] have only been obtained by removing a portion of the brain
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of epileptics, not a trivial procedure"  ( 5 ).  So far, the process has not been successful in guiding

the adult stem cells to the correct area of the brain for replenishment.  In addition to this problem,

the quantity of adult stem cells in the brain is not large enough to be isolated and extracted easily.

While this process has the potential to succeed in the future, so does the use of pluripotent stem

cells for a similar procedure.  The brain controls the only cells in the body that cannot be replaced

because it contains our individual identity.  However,  through the use of embryonic stem cells it

will be possible to rejuvenate the cells.  Unlike Dr. Scharfmanís studies, the procedure would not

require a portion of oneís brain to be removed in order to extract the stem cells. The patient of

pluripotent stem cell transplantation would only require an injection of his own stem cells for

rejuvenation to occur.

        Many potential benefits of pluripotent stem cells have been cited, but the truth is that

scientists are more motivated to understand the structure of these cells. Pluripotent stem cells

will provide scientists with a glimpse into the complex events that take place in the human body.
    direct
"A better understanding of normal cell processes will allow us to further delineate the fundamental

errors that cause these often deadly illnesses"  (NIH  3).  When the mystery of cell mutation is
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uncovered, it would be possible to figure out why some mutations lead to cancer.   "A primary

goal of this work would be the identification of the factors involved in the cellular decision-making
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process that results in cell specialization"  ( 3 ).  Drug development and testing would also be

affected by the understanding of normal cell structures.  For example, instead of using human

subjects for initial drug tests, human cell lines could be used instead.  This procedure, using

cell lines, is currently being conducted for cancer cells.  The use of cell lines allows the testing of

new medicine to be done more quickly, which will help develop the drugs quickly as well.  Using

cell lines will not eliminate human and animal testing, but it will provide scientists with an

opportunity to first exam the safety and usability of the drugs before performing clinical trials
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with live subjects  (3).  Even a greater ambition of pluripotent stem cell research is reversing

the aging process.  Dr. West insists that "the great hope is to be able to make young cells,<<direct
                                                          word omission
tissues and organs for the treatment of aging [. . .]" (Fahy and Kent  40).  Understanding how cells

differentiate is pivotal in solving the question of why we grow old; revealing the mysteries of this

topic would be discovering holy grail of the medical field.

         Although research with adult cells, umbilical cord blood, and Parthenogenesis shows

promise, pluripotent stem cell research could be considered the pinnacle of advanced medicine

with no limitations.  As it is currently understood by the scientific community, adult stem cells of

any kind are limited in their capability to be modified easily.  Pluripotent stem cells, embryonic

stem cells and embryonic germ cells, have a great modification capacity, and are thought to be

to many more, possibly all, cell types and tissues,' "  agrees Dr. Berg who is Cahill Professor of

Biochemistry, Emeritus, and Director of the Beckman Center for Molecular and Genetic Medicine
                                                       qwq
at Stanford University Medical Center.  " 'It is this pluripontentiality that makes the embryonic cell

so promising for both a basic understanding of differentiation and for the development of cell

therapies, which may be the best direstion to take for eliminating life-threatening diseases and

making life more promising for those afflicted' "  (Robinson  7).

                                         Works Cited

American Association for the Advancement of Science and Institute for Civil

        Society. "Stem Cell Research and Applications: Monitoring the Frontiers

        of Biomedical Research."  Nov. 1999: 1-6.

American Society of Hematology. BONE MARROW STEM CELL MAY PRESENT

        ALTERNATIVE TREATMENT FOR HEART ATTACK VICTIMS. Dec. 7 2001.

        19. Feb 2002. <http: //www. hematology. org/news/pres s-bonemarrow.cfm>.

Fahy M. Gregory, Kent Saul. "THERAPUTIC CLONING UNDER FIRE." Life

        Extension  March 2002: 39-47.

Joseph, Jenifer. "Growing The Ultimate Cell." ABCNEWS.com. 5 Nov 2001.

        8 Mar. 2002. <http://abcnews.i-,ro.com/sections/l-lvin2/ews/stemcells.html>.

Kent, Saul. "DON'T Let The U.S. Government Ban Therapeutic Cloning." Life

        Extension  March 2002: 50-57.

Lemer, Jane. "Doctor gets grant for stem-cell research." The

        JournalNews.com 14 Jan. 2002. 19 Feb. 2002.

        <http://www.thejournalnews.com/newsroom/0/stemcells.html>.

Lopez, Kathryn Jean. "The Truth About Stem Cells." National Review online

        26 Feb. 2001. 21 Feb. 2002.

        <http://www.nationalreview.com/interrogatory/interrogator/ shtml>.

National Institute of Health. Stem Cell: A Primer May 2000. 30 Jan. 2002.

        <http://www.nih.gov/news/stemcell/primer.html>.

O'Mathuna, Donal. "Cloning and Stem Cell Research Wrong Movies on Both

        Sides of the Atlantic." A Center for Bioethics and Human Dignily Paper.

        Fall, 2000. 2 Feb 2002. <http://www.cdhd.org./newsletter/002/002omathuna.html>.

Pollack, Michael. “The Importance of Parthenogenisis.” The Journal Of

         Nueroscience Research 45 (Spring 2001): 28-34.

Robinson, B.A. "Human Stem Cells." ReligiousTolerance.org Aug. 29 2001.

        19 Feb 2002.  <file: //A:\Human stem cell research.html>

Stolberg, Sheryl Gay. "Scientists Urge Bigger Supply of Stem Cells." New York

        Times  11 Sep. 2001: n. pag.

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