1 gender and traits selection prior to conception : ethical issues binf705 –research methods ...

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Gender and Traits Selection prior to conception : Ethical Issues

BINF705 –Research Methods

Presented by Sugandha Sharma

Yingqi Liang

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CNN report - Gender selection a reality, but is it ethical?

Matthew and Beth Mandolesi told their doctor that they would be happy with a boy or a girl but wondered if there was a way to increase the odds that it would be a boy.

Five years later, they are the parents of two boys, Antonio and Angelo.

The Mandolesi family is part of a growing trend called "family balancing" that allows couples to choose their baby's gender, Matthew and Beth Mandolesi said they are happy with their decision.

"At the time we did it, we didn't really think about the ethical part ...," Matthew said. "We've heard both sides since then. ... If we had to do it all over again, we would do it again."

http://www.cnn.com/2005/HEALTH/conditions/11/16/pdg.gender.selection/index.html

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Is the gender pre-section technology used as an instrument of gender discrimination?

Will the preference of one gender over the other, in this case boys over girls, create a future imbalance of population and power?

Should gender pre-selection technology only be used with genetic screening?

Should gender pre-selection technology be allowed to use for creating ‘Family Balancing’?

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Gender Selection History

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Gender Selection History – Mythical methods

Many sex selection recipes since early centuries

Unscientific sex selection methods

The mythical methods to have a son

– The man should wear boots to bed, get drunk, hang his pants on the right bedpost, bite his wife’s right ear.

– The woman should lie on her right side after sex, eat red meat or sour foods, let a small boy step on her hands or sit on her lap on her wedding day.

– The couple should have sex in dry weather, on a night with a full moon.

There were many ‘interesting’ recipes used by many couples for years Ref: http://8e.devbio.com/article.php?ch=21&id=185

http://8e.devbio.com/article.php?ch=21&id=185

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Gender Selection History–Gender Prediction Chart from Ancient China

《中国古代的生男生女示意表》

Ref: http://www.xjw.cn/slsn.htm


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Gender Selection History - Infanticide

When mythical remedies didn’t work, Infanticide was used as a way of sex selection

What’s Infanticide?

– the practice of intentionally causing the death of an infant of a given species, by members of the same species - often by the mother. More recently in criminology, it includes various forms of non-maternal child murder.

Infanticide became the only solution for a child of the unwanted sex.

Infanticide had been practiced in different parts of the world for many years.

The practice has become less common in the western world, but continues today in areas of extremely high poverty and overpopulation, such as parts of China and India. Female infants, then and now, are particularly vulnerable.

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Gender Selection History - Infanticide

Case study on female Infanticide in India– in rural India, the centuries-old practice of female infanticide can still be considered a wise

course of action." (Dahlburg, "Where killing baby girls 'is no big sin'," The Los Angeles Times [in The Toronto Star, February 28, 1994.])

– According to census statistics, "From 972 females for every 1,000 males in 1901 ... the gender imbalance has tilted to 929 females per 1,000 males. ... In the nearly 300 poor hamlets of the Usilampatti area of Tamil Nadu [state], as many as 196 girls died under suspicious circumstances [in 1993] ... Some were fed dry, unhulled rice that punctured their windpipes, or were made to swallow poisonous powdered fertilizer. Others were smothered with a wet towel, strangled or allowed to starve to death."

– The bias against females in India is related to the fact that "Sons are called upon to provide the income; they are the ones who do most of the work in the fields. In this way sons are looked to as a type of insurance. With this perspective, it becomes clearer that the high value given to males decreases the value given to females

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Infanticide was practiced in Ancient Greece, the early Roman Empire and in the Arab world.

Several laws and religious groups had tried to stop this process.

Preventing Infanticide was not efficient until after laws had became stricter.

– Ref: http:// www.gendercide.org/case_infanticide.html


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Gender Selection History – Other Scientific Techniques

Other Scientific techniques such as ultrasound screening and amniocentesis became available.

These techniques not only can provide appropriate prenatal care for an unborn child, but can also reveal the sex of a child, which should ideally not affect the treatment of an unborn child.

According to an India survey, in 1985 Bombay, 96% of all aborted female fetuses were done so after amniocentesis analysis revealed the sex of the child.

These techniques have been used in known abortions in countries favoring sons, such as India and China.

– Abortions are considered legal in most counties including the U.S in the first trimester

– It’s hard to prevent sex selective abortion as there is no way to tell the difference between whether a parent does not want the child at all or whether he or she does not want it because of the fetus’ sex.

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Gender Selection History –More Scientific Recipes

After leaning more about the mechanisms and reproduction in recent years, scientist came up with “ more scientific” recipes.

None of “ more scientific” recipes were exactly proven.

Example of those recipes

– Shettles, Landrum and David Rorvik 1970 • Based on the fact that androgenic (male producing) sperm is smaller and swims faster

than the gynogenic (female producing) sperm, they hypothesized that couple having sex close to the time of ovulation have greater chance of having a son than couples having sex several days prior to the ovulation.

– Stolkowski and Choukroun, 1981 • The Internal ionic milieu of the female genital tract may influence the type of sperm that

can reach the egg. A woman who wants a son should eat food high in sodium and potassium. To have a girl, woman should eat foods rich in calcium and magnesium.

• Ref: http://www.pjbs.org/pjnonline/fin554.pdf

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Gender Selection History –Sex Pre-selection

The use of technology for sex selection maybe accelerated by the introduction of sexual pre-selection techniques.

There are three types of selective technologies

– Sperm Seperation

– Sperm sorting

– pre-implantation genetic diagnosis, or PGD

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Modern Technologies for Sex Pre-Selection

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Modern Technologies for Sex Selection

three types of selective technologies– Sperm separation (Ericsson’s Sperm Sorting method) - The first and the

oldest type

– Sperm sorting ( Flow-Cytometry Separation) -- more sophisticated type

– pre-implantation genetic diagnosis, or PGD -The newest and most controversial method

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Modern Technologies – Sperm Separation

Sperm Separation (Ericsson’s Sperm Sorting method)

– Montana-based lab called Gametrics in 1970 developed the method led by Dr.Roland Ericsson. It’s also known as Ericsson’s Sperm Sorting method.

– Relies on differences in sperm swimming-speeds due to x chromosomes weighing more that Y chromosomes.

– Y Chromosome-carrying sperm swims faster.

– Licensed for use in livestock breeding only.

– Enhanced to include human sperm separation.

– Was only capable of “enriching” sperm at a rate 10% less reliable than another popular technique using flow cytometry, also known as sperm sorting.

– “The method that Matthew and Beth Mandolesi chose gave them about a 60 percent chance of having a boy, according to their fertility doctor. “

– “The couple paid $250, in addition to the cost of an in vitro fertilization procedure. The average sperm sorting costs $400 to $600 today.”

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Modern Technologies – Sperm Sorting

Sperm Sorting (Flow-Cytometry Separation)

– Laser beams are passed across a dyed sperm and separated according to weight.

– Sperm that have been dyed are separated through a cytometer after which separation occurs based on the proportion of light emitted by the sperm.

– MicroSort, from the Genetics & IVF Institute of Fairfax, Virginia, has been in clinical trials since 1995, hoping to gain approval from the Food and Drug Administration. It claims 76 percent accuracy for boys and 91 percent accuracy for girls.

– The director, Sherman Silber stated, “Finally someone has developed a method of sex selection that is honest and not a fraud, because everything prior to MicrosSort has been clearly in error or frankly fraudulent.”

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Modern Technologies – pre-implantation genetic diagnosis

Pre-Implantation Genetic Diagnosis (PGD)

– The newest and most controversial method.

– Based on embryo examination.

– First developed and is used primarily to find genetic mutations linked to about 200 genetic diseases such as Tay-Sachs and cystic fibrosis.

– Eggs are taken from the woman and fertilized with sperm to form an embryo. Doctors then take one cell out to analyze its DNA. The healthy embryos are selected, and then female or male embryos can be chosen.

– “This method requires in vitro fertilization. It's 99 percent effective and costs up to $19,000, said Dr. Jeffrey Steinberg of the Fertility Institutes, whose clinics in Los Angeles, California; Las Vegas, Nevada; and Mexico provide sex selection through various methods, including PGD.”• http://www.cnn.com/2005/HEALTH/conditions/11/16/pdg.gender.selection/index.html




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Modern Technologies

Will modern technologies like PGD being used for elective, non-medical reasons?

– Dr. Mark Hughes, a pioneer in PGD and director of the Michigan-based Genesis Genetics Institute, says that 70 percent of patients who are using PGD for gender selection wouldn't have needed in vitro fertilization in the first place.

– That means healthy, fertile couples are choosing this higher risk, expensive, sometimes painful process when they could conceive otherwise.

– Like the controversy associated with embryonic stem cell research, there are concerns over what happens to the unused embryos created by PGD.

– "It probably isn't an ethically good thing to do because you're creating embryos when you know you won't use half of them," said Winslow of the Florida Institute for Reproductive Medicine.

– Some bioethicists say they also are concerned about the use of the technology as an instrument of gender discrimination.

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Culture Views

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Culture Views Toward Gender Preference

A 2001 article in the British Medical Journal claims that “ in Western society there are as many couples who want the girl as there is who want the boy”.

Some eastern nations, such as India and China, showed strong preference toward males.

– In some parts of China today, women are still pressured by their husbands and their families to give birth to boys.

– "In China now, there are 117 boys for every 100 girls. In parts of northern India, it's 140 boys for every 100 girls," says Michael Sandel, a Harvard University professor and member of the President's Council on Bioethics.

– In India, daughters are seen as an expense due to the tradition of paying dowries when daughters marry.

– A report states that women in India express a preference for sons, primarily for financial reasons. This preference reflects the subordinate position of woman in this society and the low economic value placed on the work of woman.

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Culture Views Toward Gender Preference

A study conducted in Malaysia found that within Malaysia, the Chinese, Indian, and Malaysian populations each have different views toward gender pre-selection.

– Malays demonstrates no sex preference, and son preference among Indians is more pronounced than among either Chinese or Malays.

– It’s interesting to compare these results to the cultural differences other three groups living together.

A 1999 report based on a 1984 survey found that the primary preference of Canadians is for at least one child of each sex.

– Among women with a sex preference, sons are preferred as first-born children.

– Canadian women with two boys have a higher probability of using contraception than woman with two girls. This could be interpreted as the desire not to have a third boy.

– Interestingly, when Canadian couples act as a unit, there is no preference for boys as first born children.

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Gender Gap

The gender gap has increased in many developing countries.

– In India, between 1950 and 2000, the number of females per one thousand males has dropped from 1053 to 972.

– The gap is increasing as a result of female neglect and feticide as well as the illegal practice of sex determination.

– The Indian health ministry has instituted legislation to regulate reproductive technologies. This move will ban preimplantation genetic diagnosis and reproductive technologies.

– According the latest news in Beijing, China has decided not to relax its one-child policy, although a family-planning official acknowledged that the policy has accelerated the nation's growing gender gap.

– At least 118 boys were born for every 100 girls in 2005, said Zhang Weiqing, minister of the National Population and Family Planning Commission. He called the imbalance, which could deprive many Chinese men of spouses in coming decades, a "very serious challenge for China.“• Ref:

http://www.freep.com/apps/pbcs.dll/article?AID=/20070124/NEWS07/701240314/1001/BUSINESS05


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PreImplantation Genetic Diagnosis and

Ethical Issues

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Key Events: Development and Acceleration of human genetic technology http://www.genetics-and-society.org /technologies/history.html

1953 - Structure of DNA deduced (Watson, Crick, Wilkins, Franklin). Concerns raised about the use of this knowledge in the future to produce genetically engineered humans.

1978 - First "test-tube baby" (in vitro fertilization)

1988 - Launch of Human Genome Project

1996 - First mammal cloned (sheep, in Scotland, by Ian Wilmut)

1997 - UNESCO adopts Universal Declaration on the Human Genome and Human Rights, prohibiting germline interventions.

1999 - Human artificial chromosomes under development

1999 - Cover stories on "designer babies" appear in Time, Newsweek, Scientific American, and many newspapers.

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Key Events: Development and Acceleration of human genetic technology

June 2000 - "Working draft" of the human genome sequence

October 2000 - A child conceived in part to provide therapeutic tissues for an earlier-born sibling is born. Techniques of preimplantation genetic diagnosis are used

December 2000 - UK newspapers report that a patent for genetically modified ("designer") sperm has been issued to fertility researchers.

August 2001 - US House of Representatives passes legislation to ban human cloning.

September 2001 - Acting Chair of the Ethics Committee of the American Society for Reproductive Medicine (ASRM) writes a letter to a fertility expert condoning sex selection using PGD for "gender variety."October 2001 - Fertility experts announce they will begin to offer PGD for use in sex selection to clients.

December 2001 - The United Kingdom's Human Fertilisation and Embryology Authority (HFEA) says that, in some cases, PGD embryos can be tested for tissue matching.

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Key Events: Development and Acceleration of human genetic technology January 2002 - Following protests, the ASRM rejects the statement of

the acting chair of its ethics committee supporting use of PGD for "gender variety," and affirms its unacceptability.

February 2002 – CLONED CAT- the first cloning of a house pet(Scientists at Texas A & M University)

March 2002 - China reportedly is created human clonal embryos for research

February 2003 - Scientists genetically modify human stem cells

April 2003 - Research on primates suggests that successful human cloning may be impossible.

April 2003 - The first complete sequence, accurate to 99.999%, of the genetic code of a single human is announced

May 2003 - A mule is cloned.

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Key Events: Development and Acceleration of human genetic technology August 2003 - A horse is cloned.

August 2003 - A rat is cloned.

February 2004 - Korean researchers announce that they have succeeded in cloning human embryos and extracting stem cells from them.

May 2004 - The birth is announced of siblings selected with the use of preimplantation genetic diagnosis (PGD) to provide stem cells for children suffering from non-genetic diseases.

http://www.newscientist.com/article/dn4965-five-designer-babies-created-for-stem-cells.html

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PreImplantation Genetic Diagnosis

InVitro Fertilization + Genetic Testing

Sperm and egg fertilized in petridish Tests to detect genetic disorders

1. Select embryos that do NOT have a genetic abnormality

detect serious single gene disorders

detect abnormalities in chromosome number

2. Select embryos that have a desired genetic trait. (tissue type

matching an ailing sibling)

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PGD applications (controversial)

Selecting embryo that is immunological match for a sick sibling

Selecting gender of an embryo in the absence of a sex- linked disease risk

Testing embryos for gene mutations associated with diseases that do not appear until later in life

Testing for mutations that indicate a heightened but uncertain risk of developing a particular disease, such as cancer.

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PGD -Limits

Not all diseases have a clearly diagnosable genetic component

Many diseases are a result of complex interaction between multiple genetic environmental factors

Sometimes, the fact that a gene is detected in the embryo does not mean that the person who developed from that embryo will definitely develop the disease

PGD does not create new genetic material, that either parent does not have. PGD ONLY allows to select among the genetic combinations present in the embryos produced.

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Is PGD Ethical? ---OPINIONS

Embryos are a unique human being, deserving of protection of a born person. So, PGD is not “therapeutic” (does not treat the condition it detects). PGD simply diagnoses a “patient” with the sole purpose of telling parents which “patient” to discard.

People not firm about the moral status of early embryo but still oppose PGD

Some argue to be wary of PGD (even if not inherently wrong or offensive) because it places society on slippery slope that will lead to genetic enhancements and human control of reproduction

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PGD ----(For arguments)

Moral status of embryo: Some believe it is lesser of the 2 evils—By allowing screening, PGD can can reduce the number of abortions, which carry greater medical and emotional consequences.

Because embryonic cells are non-differentiated, the embryo is not clearly individual, and so no life is taken by terminating these embryos.

Other providers advertise and believe that parents should have the freedom to decide what uses of PGD are appropriate to their particular needs

Some observers argue that parents try to give every possible advantage to their children. So PGD should be viewed as such a technology.

The cost of rearing child with late-onset of disease may be financially and emotionally significant, and may be the heart of couple’s decision to reproduce at all.

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PGD ----(Against arguments)

Pro-life activists argue that life begins at fertilization and not conception. So embryos entitled to same legal protections afforded to individuals.

Some providers believe certain uses such as gender selection of embryo for non-health related reasons is unethical

Some suggest that PGD should be used to avoid serious genetic disease, but inappropriate to detect mild conditions or benign traits. Use PGD when suffering outweighs the risks involved and concerns over status of embryo.

Late-onset of disease:Some question the use of PGD to screen embryos for diseases that will not affect the person until adulthood (ex: Huntington disease). Children born will enjoy several decades of normal health before symptoms appear……science may find a treatment or cure.

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Safety, Accuracy , and Effectiveness Is the procedure safe for mother and resulting child?

Does it accurately detect the genetic mutation of interest?

Is it effective in producing a child free of disease?

IVF Risks: In all IVF processes there are risks associated with hormones used to stimulate ovulation

There is risk the procedure could result in ectopic pregnancy

Because more than 1 embryo is transferred, there is heightened risk that mother will carry multiple fetuses which can make for higher risk pregnancy

No certainty that pregnancy will occur

Known PGD Risk: Biopsy to remove 1 or 2 cells from the embryo for genetic testing may harm or destroy the embryo.

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Current Oversight and Policy approaches Very little oversight; Decisions left to providers; done on case basis

Ambiguous and complex regulatory status

3 federal agencies in US Dept. of Health and Human Services

– Centers for Disease Control and Prevention: oversees 1992 Fertility Clinic Success Rate and Certification act (FCSRA). Clinics report variety of data including pregnancy success rates, but not health status of bies born.

– Food and Drug Administration: under the Federal FD& Cosmetics act regulates drugs, devices used in IVF treatments. May require submissions. FDA does not regulate most genetic tests, but regulates certain components used in the tests.

NO UNIFORM SYSTEM TO ASSURE ACCURACY OR VALIDITY BEFORE TESTS ARE MARKETED.

FDA has also not determined that reproductive tissues are biological products when used for IVF or PGD procedures.

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– Center for Medicare and Medicaid Services: implement the Clinical Laboratory Improvement Amendments of 1988 (CLIA). CLIA includes requirement for lab personnel, documentation, validation of tests and procedures, and monitoring lab performance. But

Not taken a position if the Labs providing IVF are “clinical laboratories”

Not taken a position if the Genetic analysis component of PGD is subject to regulation as clinical labs.

Not established proficiency testing requirements for molecular genetic testing.

SO…RESPONSIBILITY TO ENSURE PROFICIENCY RESTS WITH THE INDIVIDUAL LABORATORIES.

STATE REGULATION: No state laws directly address PGD

Current Oversight and Policy approaches

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Identifying a piece of Y – chromosome => 85-95 % accuracy of gender

Ethical Concerns:– Perpetuation of gender oppression

– Appropriateness of expanding control over non-essential characteristics of children

– Unfair expenditure of limited medical resources

American Society for Reproductive Medicine (ASRM) (May 2001)– “ethical for parents to choose children’s sex for non-medical reasons”

– “ethical for parents to use the technology to select for a child “of opposite gender to that of existing child/children”

– Ethical for parents to have their first child of a particular gender

THEY WERE REFERRING TO SPERM SORTING TECHNIQUES BUT THIS OPENED THE

FLOOD GATES FOR USE OF PGD.

CHR FERTILITY CLINIC BEGINS OFFERING PGD. THEIR LOGIC : IF ITS ETHICAL TO IMPROVE THE ODDS OF GENDER SELECTION, THEN ITS ETHICAL TO

USE PGD WHICH IS NEARLY 100% EFFECTIVE.

Revised later: “…initiating IVF and PGD soleley for non-medical gender selectioin, or to

create gender variety in a family should be discouraged”

PGD and Gender Selection of embryos

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PGD and Gender Selection….

Leads to gender discrimination---Primary reason for Prohibition

Gender discrimination occurs in Middle East, and Asia

No data for gender discrimination in the US

Decentralized health care system in the US--will unlikely deprive others of medical resources

In the US generally used for “balancing family”

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PGD and selecting nonmedical traits (modern eugenics) Eugenics is a social philosophy which advocates the improvement of human

heriditary traits through various forms of intervention.

– Micromanaging child’s inherited traits

Selecting for physical, or psychological state --intelligence, height, or musical talent - NOT currently possible But demand is there.

“human race faced with genetic deterioration unless we intervene in repruductive decisions”

Behavioral genetics researchers LINK genes to complex behavior example: alcoholism, bipolar disorder. --Polygenic traits, and influenced by environment. Cannot test for these traits.

Couples have free will to determine when and how to have children. Free will to procreate, and select for non medical traits. “It is not disease, but its impact on well being”. If intelligence affects well-being then parents should select.

Critics: circumventing natural random process of evolution; selecting for non-disease traits leads to commodification of children; Paid for perfect child and anything less than perfect is not acceptable.

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Extracting a cell from a budding human embryo can expose genetic defect, but does it actually help generate more healthy babies?– The First Cut: Nature 445:479-480

Traditional view of embryologists: First few cells of embryos are essentially equivalent, remove 1-2 and the rest can fill the gap

Recent studies challenge this idea, and believe that “early cells are predisposed to contribute in different ways to future tissues”.

– Histone arginine methylation regulates pluripotency in the early mouse embryo.

Nature 445: 214-218(2007)

PGD and missing parts?

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References



http://www.xjw.cn/slsn.htm

http://www.gendercide.org/case_infanticide.html

http://www.pjbs.org/pjnonline/fin554.pdf



http://www.genetics-and-society.org/technologies/history.html

Genetic Testing of Human Embryos: Ethical Challenges and Policy Choices

– Kathy Hudson, Susannah Baruch and Gail Javitt (The Genetics and Public Policy Center, Berman Bioethics Institute, JHU)

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References (contd)

Customizing Conceptio: A survey of preImplantation Genetic Diagnosis and the resulting social, ethical and legal dilemmas

– Jason Christopher Roberts (2002)

The First Cut: Nature 445:479-480

Histone arginine methylation regulates pluripotency in the early mouse embryo. Nature 445: 214-218(2007)

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