EngCmp
Final Paper
Genetically my brain to make me a faster writer, please...
In the latter portion of the twentieth century, Rabbi Josef Ekstein lost four of his eleven children to a debilitating hereditary condition known as Tay-Sachs disease. Following his losses, Ekstein began a righteous campaign to expel Tay-Sachs from the Ashkenazim Jewish community. Working with geneticist Michael Kaback and other ultramodern scientists of his day, Ekstein constructed a revolutionary prenatal screening program where members of the community had the option of having their blood drawn and tested for the presence of protein markers unique to Tay-Sachs (Wingerson, 1998). In his community, where arranged marriage was traditional practice, if both members of a newly arranged couple had previously tested positive and were determined to be Tay-Sachs carriers, either matchmakers would reject the newly formed engagement based on the notion of carrier states “blemishing” a family’s background, or genetic counseling was made available where healthcare and social workers, acquainted with the disease process and it’s effect on families, worked with and educated the couple to assist them in making wise, calculated decisions regarding abortion and alternative means of conception (Wingerson, 1998).
Because abortion was considered taboo in Ekstein’s orthodox community except when the mother’s life was in peril, opponents and conservative Rabbi’s screamed “foul!” They rejected Ekstein’s logic that giving birth to several affected children was perilous to a mother, and shot down the notion of rejecting otherwise felicitous marriages principally based on ambiguous criteria (Wingerson, 1998). He famously noted after the initiation of his venture, “I got no cooperation, there was total opposition. The entire mentality was that you couldn’t even talk about screening” (Wingerson, 1998).
Despite the contention, however, Ekstein’s forward thinking and contemporary screening model proliferated not only among constituents of his community, but across the greater portions of North America (Wingerson, 1998). Since 1983, there has been a significant increase in genetic screening and a proportional decline in the occurrence of Tay-Sachs disease (Wingerson, 1998). Furthermore, statistics have shown the results of the higher incidence of prenatal screening, and indicate there have been less than five newly diagnosed cases of Tay-Sachs in the United States and Canada annually since that same year (Wingerson, 1998).
Disease, in the context understood by the healthcare community, is any process that results in the abnormal functioning of any organ, structure, or system (Porth, 2005). Tay-Sachs, for instance, is a disease in which genetic variation results in the malfunction of a single chemical necessary for normal brain metabolism (Porth, 2005). Because these newborns lack the genes responsible for coding beta-hexosaminidase-A molecule: fatty acids accumulate in nerve cells, nerve degeneration ensues, and what were charming, babbling children transform into “drooling, immobile children with blind eyes and overlarge heads” (Wingerson, 1998). In most instances, affected children are dead before the age of six.
Now, fast-forward to the twenty-first century, to an era where breakthroughs in genetics and microscopic imaging technology, in conjunction with a heavy purse and modern wisdom, set the stage for the completion of the Human Genome Project. This project went far enough to establish the mutations and abnormalities responsible for a diverse range of hereditary diseases such as Tay-Sachs, Cystic Fibrosis, and Sickle Cell Anemia (Boon, 2002). Nobel Prize laureate Walter Gilbert, and the leader of the National Institute of Health’s role in the enterprise, Francis Collins, predicted by 2010 the project will have determined the genetic profiles of approximately 2000 to 5000 illnesses “giving us an almost complete understanding of the genetic basis of ancient diseases” (Boon, 2002). Furthermore, Bill Clinton exclaimed after the completion of the project that it “promises to lead to a new era of molecular medicine, an era that will bring new ways to prevent, diagnose, treat, and cure disease” (Boon, 2002).
We have had the resources and appropriate systems available to offer prenatal screening to couples to estimate their probability of passing on several disease traits, and modern breakthroughs in genetics related to healthcare has extended our scope of medical practice to concretely diagnose fertilized embryos with hereditary or chromosomal disorders.
Despite blood and serum testing being considered revolutionary in Ekstein’s day, it is now principally used as a preliminary adjunct too much more accurate and efficient forms of prenatal screening; that is if a mother or father is determined to be a carrier of a hereditary disease through blood typing, they will be referred to more specialized healthcare providers for more accurate forms of diagnostic testing. Comparative Genomic Hybridization, for example, has superceded blood typing as the principal form of prenatal screening. This procedure goes beyond determining the Punnett risk of passing on a disease trait; rather, it analyzes the chromosomes in an embryo to definitively determine the presence of chromosomal abnormalities or mutations (Moorthie, 2008).
In conjunction with this contemporary science, in vitro fertilization and the applicability of genetic engineering, which is regarded as the tangible form of molecular medicine prescribed by Clinton to treat and cure illness, becomes obvious: implant an embryo free of disease, or fix the underlying genetic abnormality present in a person affected by a hereditary condition (McKibben, 2003). Despite this, skeptics like Lee Silver object. They accept McKibben’s proffer, but claim that genetic engineering can go one step further and can be used to manipulate and improve the genome of germ cells before fertilization. They advocate the use of germline engineering to create a future where people can be liberated from threats like disease, a future where current methods, such as in vitro fertilization and somatic gene therapy, are eclipsed by more effective and radical methods of genetic engineering. However, opponents to Silver’s objective claim that current methods of genetic engineering are sufficient to treat disease, and they question the ethics of pursuing Silver’s ambitious goals. These proponents contend that current methods should be used, but argue against allowing genetic engineering to evolve into Silver’s ambitions because human cloning, which is necessary to achieve germline engineering, are too unethical to be done. Somatic gene therapy, and in vitro fertilization used in conjunction with prenatal screening, are paramount to treating disease and through proper legislation, which would establish the relevant ethical criteria and parameters for practicing genetic engineering, can control human cloning and thus the speculative evolution of genetic engineering to germline engineering advocated by scientists like Silver.
For those unfamiliar with in vitro fertilization, the basic tools necessary for a successful carriage and pregnancy are as follows: a viable ovum, sperm, and a uterus that can maintain pregnancy. The application for preventing hereditary disease is essentially: the ovum is fertilized by the sperm outside of the womb, the fertilized embryos are assessed for the relevant genetic mutations or abnormalities, and the unaffected embryos are implanted into the mother. After acknowledging the benefit and risk outcomes identified during genetic counseling, a stepwise process that is used for in vitro fertilization could then be initiated.
Tay-Sachs and Ekstein’s model consolidated with modern techniques and science forms a hypothetical paradigm illustrating the use prenatal screening and in vitro fertilization can have to treat disease. Consider, for a moment, a population of one hundred couples trying to conceive where both the male and female test serum positive for carrier states of Tay-Sachs. Punnett square analysis of this autosomal recessive disease shows that if every couple succeeded in conceiving, twenty-five children would be born with the condition. The proposed model would proceed as follows:
First, couples would participate in genetic counseling where they would be educated on the following options: proceed with natural pregnancy and birth, or choose in vitro fertilization. If the parents prefer the latter choice, genetic counselors would educate them on the risks and benefits of in vitro fertilization. For example, the benefits would include a healthy child unaffected by Tay-Sachs, and the risks would include miscarriage. Prior to implantation of embryos in a mother’s womb, comparative genomic hybridization would be used to detect mutations among the HEXA genes on chromosome fourteen, the aforementioned allele responsible for coding the beta-hexosaminidase-A molecule (Human Genome Project, 2008).
For those unfortunate individuals already born with a hereditary condition, other forms of therapy, for instance somatic gene therapy, can be used to treat their disease. Tay-Sachs disease will again be used to show the efficacy of somatic gene therapy:
Transgenic methods of genetic engineering can be used to replace or fix mutated chromosomes responsible for a person’s condition (Wingerson, 1998). Similar to how the HIV virus is able to replicate, integrate, and express its viral RNA in a host cells genetic sequence forming functional viral DNA, exogenous, healthy HEXA genes obtained from genetically matched donors can be introduced to the affected person by a number of vectors, such as non-virulent bacteria or viruses. The use of existing immunosuppressant drugs, in conjunction with a relatively low risk for rejection related to the genetic match, results in a very real, and very high probability that the exogenous HEXA gene will be accepted and integrated by the person genome following initial exposure. Furthermore, using relevant pathophysiologies of similar processes as archetypes, such as the HIV replication and integration cycle in creating it’s own viral DNA, if the transgene is able to assimilate with the host, replication and expression of the gene will naturally occur. If this takes place, the healthy genes will provide for grossly normal brain metabolism and the person will not exhibit the manifestations and premature death associated with Tay-Sachs disease.
Other microcosmic examples that present the potential of in vitro fertilization and somatic gene therapy in treating certain health disparities are Cystic Fibrosis and Sickle Cell Anemia.
According to recent epidemiologic surveys, Cystic Fibrosis is the most common autosomal recessive disorder among people of European descent (Human Genome Project, 2001). The Human Genome Project (2001) determined the etiology of this disease to be the deletion of three essential base pairs in the CFTR gene. As a result of this mutation, the normal balance between sodium and chloride ion channels is disturbed, and the affected person produces thick mucus that cannot be removed by normal ciliary functions (Porth, 2005). The accumulation of mucus in the patient’s lungs, pancreas, liver, intestines, and other organs results in susceptibility to frequent, recurring infections and debilitating manifestations that inevitably progresses to multisystem failure (Porth, 2005). The course of the disease has a poor prognosis: patients have an average lifespan of less than forty years.
Sickle Cell Anemia is a hereditary disease that is prevalent among millions of people worldwide (Human Genome Project, 2003). Although manageable in most cases, manifestations related to this particular condition include periodic breakthrough pain, stunted growth, and high susceptibility to embolic strokes. The Human Genome Project (2003) has already established several mutations in the beta-hemoglobin gene located on chromosome eleven that is responsible for this illness. The most common of which is the allocation of normal hydrophilic glutamic acid by hydrophobic amino acids at various positions along the polypeptide chain (Human Genome Project, 2003). Because of the hydrophilic nature of the substitutes, the protein structures of hemoglobin chains cannot be maintained, resulting in the clumping of hemoglobin molecules and the classic sickling of circulating red blood cells (Human Genome Project, 2003).
Similar to Tay-Sachs disease, it is common practice for newly pregnant women to seek prenatal screening to assess for potential complications correspondent to their pregnancies. Several of the methods sought after by these women, such as blood screening, are effective in early indication of both Cystic Fibrosis and Sickle Cell Anemia. Despite cognizance of an underlying disease process, however, early diagnosis does not translate to a treatment or cure.
If human in vitro fertilization or somatic gene therapy were to be commonly practiced, the same principles applied to treat the underlying genetic components of Tay-Sachs could be used to treat every other understood chromosomal or hereditary abnormality: choose an embryo devoid of the mutation, or introduce healthy forms of the gene to supplement the mutated genes function. After initial diagnosis, parents or affected people would participate in genetic counseling and, if favored, embryos negative for mutated CFTR genes, mutated beta-hemoglobin genes, etc… would be implanted, or people living with hereditary conditions would undergo somatic gene therapy.
There have already been a few, isolated cases where somatic gene therapy has been successful. In Redesigning Humans: Our Inevitable Future, Gregory Stock (2002) provides a real example where a young girl, Natalie, was diagnosed with a hereditary disease, Fanconi Anemia. Those unfamiliar with this process should know that it is an autosomal recessive genetic disorder, similar to Cystic Fibrosis, Sickle Cell Anemia, and Tay-Sachs, and has a very poor prognosis generally causing cancer, complete bone marrow failure, and death well before adulthood (Porth, 2005). The parents, after speaking with genetic counselors regarding their options, chose to conceive another daughter hoping the cells, derived from the child’s umbilical cord, would be a genetic match for cell transplantation (Stock, 2002). In the end, the couples calculated decision, and the genes from the mesenchymal cells harvested from the daughter’s umbilical cord, corrected Natalie’s condition, according her a new lease on life (Stock, 2002).
The aforementioned applications of in vitro fertilization and somatic gene therapy are within our scopes of scientific knowledge and technological capabilities and McKibben, as well as other like-minded scientists, acknowledge their approval and recognize the clinical applications of these methods (McKibben, 2003). Other scientists like Lee Silver, however, advocate another type of genetic engineering referred to as germline engineering where germ cells (i.e. sperm and ovum) are genetically manipulated prior to fertilization; where genes and chromosomes are subtracted and added to a person’s genome as favored (McKibben, 2003).
Referring back to the accomplishments of the Human Genome Project, our genetic sequence has already been established, and according to geneticists and molecular biologists Gregory Stock and Lee Silver, advances in genetics, technology, and genetic engineering will allow us the capability of writing our physiological and anatomical codes like a word document (McKibben, 2003). Along the lines of this metaphor, allowing germline engineering to evolve into fruition will allow us to effectively ‘delete’ those chromosomes in our body responsible for hereditary diseases, and ‘delete’ those genes responsible for undesirable traits like obesity and poor intelligence. We will be able to ‘write’ instructions for more muscle mass and perfect physiques, we will ‘write instructions’ for higher intelligence, parents will be able to ‘write’ the instructions for a child in their image (McKibben, 2003). What Silver and Stock are advocating is using germline engineering as a form or eugenic engineering, where designer babies can be manufactured in which undesirable traits are substituted for desirable ones (McKibben, 2003).
A medical related example of how germline engineering can be used related to immune function is HIV, and the body’s natural immune response. The HIV virus is coated in a viral envelope that mimics human cell membranes making it nearly indistinguishable from other bodily cells; however, it has unique viral glycoprotein surface complexes necessary to attach to host cells (Porth, 2005). As of now, the bodies natural immune function cannot distinguish between the viral cells and host cells, but through germline engineering, it might be possible to make the host’s natural immune system more sensitive to these surface proteins. If the body can recognize the foreign virus from the onset of primary exposure, it is quite possible to prevent the possibility of HIV being able to infect humans.
Although this form of genetic engineering advocated by Silver may seem desirable to some, to cure HIV for example, there is one fundamental step that is a foundation of the argument against it. In order for science to accomplish germline engineering, a radical piece of technology has to exist: the ability to clone people (McKibben, 2003). Lee Silver admits, “Without cloning, genetic [germline] engineering is simply science fiction. But with cloning, genetic engineering moves into the realm of reality” (McKibben, 2003).
The notion of human cloning, from an ethical perspective, has been argued among scientists and geneticists ever since the prospect of cloning was taken out of science fiction and introduced into reality with the successful cloning of Dolly the sheep. The prospect of human cloning, however, and the inherent risks to subjects involved, is contradictory to the ethical codes regarding the use of humans for research.
The Nuremburg Code, created following recognizing Hitler’s abhorrent eugenic experiments on humans, stresses the fundamental principle that “Voluntary consent of the human subject is absolutely essential” (Shanks, 2005). In addition, the subject’s consent has to be obtained without any form of “force, fraud, deceit, duress, overreaching, or other ulterior form of constraint or coercion” (Shanks, 2005). Next, The Declaration of Helsinki, an adjunct purposed to elaborate on the Nuremburg Code, established the principal that any minute risk a human subject might experience during research must be in proportion to the objective of the study (Shanks, 2005). To be clearer, it states that, “In research on man, the interest of science and society should never take precedence over considerations related to the well-being of the subject” (Shanks, 2005). Last, The Belmont Report maintained three basic principals for human subjects for research:
1. Respect for persons – the rights of the research subjects, especially those with diminished autonomy and capacity
2. Beneficence – research must not only avoid harming those involved but must also be intended to help
3. Justice – just distribution of potential benefits and harms and fair selection of research subjects (Shanks, 2005)
The President’s Council on Bioethics summarized these three principles applied in conjunction with one another, stating:
When applied, these general principles lead to both a requirement for informed consent of human research subjects and a requirement for a careful assessment of risks and benefits before proceeding with research. Safety, consent, and the rights of the research subjects are thus given highest priority (Shanks, 2005).
Because human clones are, as the name implies, human, these codes creating foundations for ethical research are applicable to them. Taking a closer look at the ethical guidelines to allow human cloning research, the impossibility of human cloning experimentation, and thus germline engineering, becomes apparent:
First, the consent required to involve a person in a study cannot be obtained from a non-existing, non-tangible person (the clone). Unlike certain medical related studies where parents are able to give consent for their child for an experimental intervention to treat a disease or condition that would otherwise disable or debilitate the child, there is no medical problem, no patient, and thus no one to obtain consent from (World Health Organization, 2005). This consideration would contradict the requirement for informed consent.
Second, animal cloning trials have established precedent indicating the inherent harms and risks posed to clones. The Word Health Organization (2008) stated in an article regarding the ethics of cloning,
Experience with animal cloning has shown substantial risks of debilitating and even lethal conditions occurring in the fetuses produced using these techniques; moreover, these problems cannot be individually predicted and avoided at this time. Some of these conditions also present a considerable risk for the gestational mother carrying the cloned animals to term.
Past animal cloning trials have produced data providing evidence for physical harm a clone might endure. For example, cloned animals have had compromised immune functions making them more vulnerable to infection and disease, susceptibility to tumors, and even death (Human Genome Project, 2008). The physical harm the human clone could sustain, as an outcome of the research is contrary to the ethical principles established by the Helsinki Code and Belmont Report giving the human subject’s safety priority.
Already, countries and other governing councils have taken the initiative to create legislation banning human cloning. They rationalize their laws and governing regulations based on the above-mentioned criteria, most notably acknowledging that the harm human clones may experience is paramount compared to the efficacy of cloning (Shanks, 2005). The most poignant example of a law banning human cloning is the Additional Protocol, formed by the Council of Europe in the 1990’s as a reaction to the cloning of Dolly. The protocol states:
An intervention seeking to modify the human genome may only be undertaken for preventive, diagnostic, or therapeutic purposes and only if its aim is not to introduce any modification in the genome of any descendents. The use of techniques of medically assisted procreation shall not be allowed for the purpose of choosing a future child’s sex, except where serious hereditary sex-related disease is to be avoided. The creation of human embryos for research purposes is prohibited (Shanks, 2005).
Additionally, the World Health Organization’s governing body issued a declaration, Genomics and World Health, stating, “Reproductive cloning would be unethical under any circumstances and that there is no ethical or medical basis for pursuing work on it” (Shanks, 2005). The United Nations issued a similar statement reflecting their view on human cloning in the Universal Declaration on The Human Genome and Human Rights, and made clear their condemnation of “Commercialization of the human genome, genetic discrimination, research without consent, and other abuses” (Shanks, 2005). These regulations, indicative of international sentiment regarding the ethics of human cloning, makes human cloning, and thus germline engineering impossible.
The clear, unambiguous language used by the Council of Europe is an example of the parameters outlining the scope of genetic engineering. Stating certain interventions are tolerable to treat disease allows, for instance the use of somatic gene therapy. Also, somatic gene therapy is tolerable according to this criteria because the genes delivered to individuals affected by certain conditions are not passed on to their offspring, similar to how HIV is not passed from infected mother to child (except through pregnancy, if the virus is able to cross the placenta or is introduced during gestation by other routes; during delivery, when the baby is exposed to the mother’s blood; or through breast feeding, the virus can get into breast milk) (Porth, 2005). Additionally, the protocol creates precedence for the allowance of genetic engineering when a hereditary disease is known to be present. Using the Additional Protocol as an archetype for future laws, legislation will be able to establish parameters for the practice of genetic engineering and in vitro fertilization. That is, somatic gene therapy can be used to treat disease, and in vitro fertilization to prevent it. Similar to The Council of Europe’s legislation, however, this archetype is forthright with its sanction of germline engineering.
The clinical applications of germline engineering are promising, for example the possibility of curing HIV, but the ethical boundaries fencing it within the realms of science fiction are too great. International demeanor and laws regarding human cloning, the essential tool to actualize the prospect of germline engineering, corresponds to a reality where the speculative evolution of germline engineering will never occur. Today, in vitro fertilization and somatic gene therapy are quintessential to current scientific knowledge and technological wisdom. Humanity already possesses the knowledge to test a fertilized embryo for disease. In vitro fertilization, in conjunction with prenatal screening, is a valuable tool for the prevention of hereditary diseases in children. For those unfortunate individuals living and dealing with the manifestations of debilitating conditions such as Tay-Sachs and Cystic Fibrosis, somatic gene therapy is parallel to a promising future. The Human Genome Project has given us the knowledge necessary to treat their disease, and existing technology has given us the capability to use viruses and bacteria to introduce normal functioning genes into their DNA, according them a new lease for a healthy life. These tools are sufficient and in vitro fertilization and somatic gene therapy paramount to treating health related disparities. Although proponents of germline engineering promise a definitive cure and promising future, opponents are too skeptical and dissented towards the idea of human cloning.
References
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