Biol 518: Presentations 3-5-03b

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Presentation on In Vitro Molecular Biology 3/5/03
In Vitro Molecular Biology Ooplasmic Transfer
Karen, Karin, Kiera, Kim

Case

March 2001: Human Reproduction journal reported that doctors confirmed up to 30 healthy children have been born worldwide whose cells contain small quantities of additional genes not inherited from either parent as a result of an infertility procedure called Ooplasmic Transfer.

Infertility procedure originated within the U.S. at the Institute for Reproductive Medicine and Science of St Barnabas in New Jersey where 15 children have been conceived.

These children have altered mitochondrial DNA (transferred inadvertently from donor), which they will pass on to their offspring.

Key Issues

1. Safety: imperfect knowledge of cell/gene function - what are the ramifications for "mistakes" made in this type of process? How will the children be affected and how can we truly know and protect both their interests and their safety? InVitro Fertilization infants appear prone to other problems - Retinoblastima and Beckwith-Wiedemann syndrome (excessive growth and inc cancer). Two cases of Turner Syndrome among Ooplasmic Transfer fetuses, high incidence, unknown cause.
2. Unanticipated Loss of Gene Line Viability: Increasing IVF appears to be increasing infertility in each generation. Theory that loss of mitochondria occurs when an excessive number genetic mutations are detected in nuclear DNA, the cell "commits suicide". We are interrupting this control process. What will that do to our viability?

3. Raises the urgency of discussion, decisions and controls relating to Inherited Genetic Modification. Crosses the line of IGM, without any oversight. FDA issued letters requiring Doctors to seek FDA approval for any fertility procedures involving alteration of human genetic materials.

Background

Ooplasmic transfer: some of the cytoplasmic material surrounding the egg nucleus of a donor cell are injected into the egg cell of the potential mother. The egg is then fertilized in vitro and implanted.

-This technique is used to aid women with infertility problems by providing "fertile" cytoplasm to condition otherwise infertile egg cells.
-Infertility procedure inadvertently introduced DNA from donor cytoplasmic mitochondria into the egg.

-Mitochondrial DNA (mtDNA) codes very specifically for only 13 genes

Structure of an animal cell
[Fig. 5.6, Biology: Life on Earth, by Audesirk and Audesirk, 4 e]

Mitochondria contain their own DNA (termed mDNA) and are thought to represent bacteria-like organisms incorporated into eukaryotic cells over 700 million years ago (perhaps even as far back as 1.5 billion years ago). They function as the sites of energy release (following glycolysis in the cytoplasm) and ATP formation (by chemiosmosis). The mitochondrion has been termed the powerhouse of the cell. Mitochondria are bounded by two membranes. The inner membrane folds into a series of cristae, which are the surfaces on which ATP is generated.

Experts and Stakeholders

Stakeholders: every human
- parents
- future generations
- medical community

Experts: geneticist, biologist, ecologist, sociologist, international community, medical professionals, including regulatory agencies such as NIH (National Institutes of Health), RAC (Recombinant DNA Advisory Committee), American Medical Association.

Values

Virtue ethics: can see end value but do not fully understand how or if genetic engineering will help humans flourish (or not). Shouldn't we fully understand the consequences of our actions before we forge ahead? Value full disclosure and discussion of issues prior to taking action.

Utilitarianism: maximization of happiness for parents - possibility of adding great benefits to human life, but at what unknown cost?

Deontology: It is the right of any parent to chose whether to alter the genetics of their offspring. IGM takes decisions away from unborn generations.

Alternative Solutions

Council on Bioethics: the enactment of an international council could address, assess, discuss, and examine ethical issues involved and advise. RAC or ELSI could take on this role.

Ban on all germ line engineering, until controls can be put in place and ramifications of research can be assessed

Collect public feedback, possibly a vote on the issue

Enact regulations with the belief that a ban will not end this type of research. (Other countries have taken this approach).

Closely monitor the ooplasmic transfer infants who were inadvertent research subjects to gain knowledge

Promote other ways of producing disease free offspring - prenatal screening

Decision Making Process

Public discussion

Examine regulation models that already exist around the world

Decisions as to relative value of individual choices based on informed consent versus legislated mandates

Screening of members who make recommendations to legislators

Consider social issues, economic issues as well as medical issues

Risk - Benefit analysis

References

Human Reproduction, Vol. 16, No. 3, 513-516, March 2001, Jason A. Barritt,1, Carol A. Brenner, Henry E. Malter and Jacques Cohen http://www.humrep.oupjournals.org/cgi/content/abstract/16/3/513

Case review by the Center for Genetics and Society BULLETIN #2 MAY 9, 2001
http://www.genetics-and-society.org/newsletter/archive/b02.html

Parens, Erik and Eric Juengst, "Inadvertently Crossing the Germ Line," Science, 292 (5516), April 20, 2001. http://www.geneforum.org/learnmore/resources/parense_juengste_20010420.cfm

Johnson, Dr. George, "Newspaper reports of genetically modified humans are misleading", On Science http://www.txtwriter.com/Onscience/Articles/mtDNAtransfer.html

Citizen Centre Report 2/17/2003, Vol. 30 Issue 4, p53, 1/3p. Number 9080836, Section: Brave New World "A Second Look at IVF"

Vladimir P. Skulachev, IUBMB LIFE, 49, 365-373, 2000 Copyright @ 2000 IUBMB "Mitochondria in the Programmed Death Phenomena: A Principle of Biology: "It Is Better to Die than to be Wrong". http://fidelio.ingentaselect.com/vl=10554184/cl=20/nw=1/rpsv/catchword/tandf/15216543/v49n5/s6/p365

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Updated 3/10/03 by thatcher@sonoma.edu

Biotechnology Presentations

Presentation on In Vitro Molecular Biology 3/5/03

	Biotechnology Presentations
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	Presentation on In Vitro Molecular Biology 3/5/03 In Vitro Molecular Biology Ooplasmic Transfer Karen, Karin, Kiera, Kim Case March 2001: Human Reproduction journal reported that doctors confirmed up to 30 healthy children have been born worldwide whose cells contain small quantities of additional genes not inherited from either parent as a result of an infertility procedure called Ooplasmic Transfer. Infertility procedure originated within the U.S. at the Institute for Reproductive Medicine and Science of St Barnabas in New Jersey where 15 children have been conceived. These children have altered mitochondrial DNA (transferred inadvertently from donor), which they will pass on to their offspring. Key Issues 1. Safety: imperfect knowledge of cell/gene function - what are the ramifications for "mistakes" made in this type of process? How will the children be affected and how can we truly know and protect both their interests and their safety? InVitro Fertilization infants appear prone to other problems - Retinoblastima and Beckwith-Wiedemann syndrome (excessive growth and inc cancer). Two cases of Turner Syndrome among Ooplasmic Transfer fetuses, high incidence, unknown cause. 2. Unanticipated Loss of Gene Line Viability: Increasing IVF appears to be increasing infertility in each generation. Theory that loss of mitochondria occurs when an excessive number genetic mutations are detected in nuclear DNA, the cell "commits suicide". We are interrupting this control process. What will that do to our viability? 3. Raises the urgency of discussion, decisions and controls relating to Inherited Genetic Modification. Crosses the line of IGM, without any oversight. FDA issued letters requiring Doctors to seek FDA approval for any fertility procedures involving alteration of human genetic materials. Background Ooplasmic transfer: some of the cytoplasmic material surrounding the egg nucleus of a donor cell are injected into the egg cell of the potential mother. The egg is then fertilized in vitro and implanted. -This technique is used to aid women with infertility problems by providing "fertile" cytoplasm to condition otherwise infertile egg cells. -Infertility procedure inadvertently introduced DNA from donor cytoplasmic mitochondria into the egg. -Mitochondrial DNA (mtDNA) codes very specifically for only 13 genes Structure of an animal cell [Fig. 5.6, Biology: Life on Earth, by Audesirk and Audesirk, 4 e] Mitochondria contain their own DNA (termed mDNA) and are thought to represent bacteria-like organisms incorporated into eukaryotic cells over 700 million years ago (perhaps even as far back as 1.5 billion years ago). They function as the sites of energy release (following glycolysis in the cytoplasm) and ATP formation (by chemiosmosis). The mitochondrion has been termed the powerhouse of the cell. Mitochondria are bounded by two membranes. The inner membrane folds into a series of cristae, which are the surfaces on which ATP is generated. Experts and Stakeholders Stakeholders: every human - parents - future generations - medical community Experts: geneticist, biologist, ecologist, sociologist, international community, medical professionals, including regulatory agencies such as NIH (National Institutes of Health), RAC (Recombinant DNA Advisory Committee), American Medical Association. Values Virtue ethics: can see end value but do not fully understand how or if genetic engineering will help humans flourish (or not). Shouldn't we fully understand the consequences of our actions before we forge ahead? Value full disclosure and discussion of issues prior to taking action. Utilitarianism: maximization of happiness for parents - possibility of adding great benefits to human life, but at what unknown cost? Deontology: It is the right of any parent to chose whether to alter the genetics of their offspring. IGM takes decisions away from unborn generations. Alternative Solutions Council on Bioethics: the enactment of an international council could address, assess, discuss, and examine ethical issues involved and advise. RAC or ELSI could take on this role. Ban on all germ line engineering, until controls can be put in place and ramifications of research can be assessed Collect public feedback, possibly a vote on the issue Enact regulations with the belief that a ban will not end this type of research. (Other countries have taken this approach). Closely monitor the ooplasmic transfer infants who were inadvertent research subjects to gain knowledge Promote other ways of producing disease free offspring - prenatal screening Decision Making Process Public discussion Examine regulation models that already exist around the world Decisions as to relative value of individual choices based on informed consent versus legislated mandates Screening of members who make recommendations to legislators Consider social issues, economic issues as well as medical issues Risk - Benefit analysis References Human Reproduction, Vol. 16, No. 3, 513-516, March 2001, Jason A. Barritt,1, Carol A. Brenner, Henry E. Malter and Jacques Cohen http://www.humrep.oupjournals.org/cgi/content/abstract/16/3/513 Case review by the Center for Genetics and Society BULLETIN #2 MAY 9, 2001 http://www.genetics-and-society.org/newsletter/archive/b02.html Parens, Erik and Eric Juengst, "Inadvertently Crossing the Germ Line," Science, 292 (5516), April 20, 2001. http://www.geneforum.org/learnmore/resources/parense_juengste_20010420.cfm Johnson, Dr. George, "Newspaper reports of genetically modified humans are misleading", On Science http://www.txtwriter.com/Onscience/Articles/mtDNAtransfer.html Citizen Centre Report 2/17/2003, Vol. 30 Issue 4, p53, 1/3p. Number 9080836, Section: Brave New World "A Second Look at IVF" Vladimir P. Skulachev, IUBMB LIFE, 49, 365-373, 2000 Copyright @ 2000 IUBMB "Mitochondria in the Programmed Death Phenomena: A Principle of Biology: "It Is Better to Die than to be Wrong". http://fidelio.ingentaselect.com/vl=10554184/cl=20/nw=1/rpsv/catchword/tandf/15216543/v49n5/s6/p365 ..
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