Fr. Joseph Howard is Member of the Executive Board of Directors of Texas Right To Life
St. John’s Hospital Ethics Committee
Director of The American Bioethics Advisory Commission
August 7, 1998
INTRODUCTION
As we approach the new millennium, scientific technology has transformed many ideas once thought to constitute science fiction into reality. Just two weeks ago, Dr. W. French Anderson–Director of Gene Therapy at the University of Southern California–announced that he will seek approval from the National Institutes of Health (NIH) Recombinant DNA Advisory Committee to attempt experiments which result in the alteration of DNA in human germ cells. The current policy of the NIH Recombinant DNA Advisory Committee does not allow for germ-line alterations but will consider proposals involving somatic cell gene transfer. Indeed, mammalian cloning has become a reality. Just recently it was reported that scientists in New Zealand cloned a cow named Lady in a final effort to save an endangered breed of cattle. Genetic tests have confirmed that Elsie is a clone of the cow Lady. The entire human genome contained in forty-six chromosomes will have been mapped and sequenced shortly after the new millennium has begun. Despite tremendous advances in the technologies of biomedical science, serious concerns of a bioethical nature have been raised and continue to be voiced. The German philosopher, Frederich Nietzche, (1844-1900) argued that once modern society and individuals became highly educated, the mere concept of Christianity would be seen as an illusion and hence destroyed. Man would then be totally free since he would no longer believe that he was bound to any type of objective moral law or code. Hence, Nietzche could claim, “God is dead. Man is now free.” Too often today many scientists and physicians have adopted a philosophical approach that is Nietzchean: they do not believe that philosophy or bioethics could possibly constitute an objective body of knowledge. Ironically, Nietzche spoke of the role of a philosopher as a physician for civilization. Some have even argued that science is amoral. Not a few have argued exactly what was set forth by Nietzche: Each man subjectively decides truth for himself and becomes a god unto himself. This Nietzchean “pride of life” of modern man serves as the foundation for the collapse of American civilization. The moral decadence of our own society is evident before our very eyes. Under the guise of the doctrine of privacy, morality becomes a “private matter” of feelings, preferences, and beliefs that need no objective justification. People argue that their “private lives” are nobody else’s business. The central assumption of this view is that there is nothing to objectively know in moral matters (Maher, 1-2). Why should we be surprised, therefore, that subjectivists argue and fight for a “right” to view and distribute pornography freely; or to use and exchange illicit drugs as well as to scandalously draw others into the world of illicit drugs; or to engage in all types of illicit and perverted sexual behaviors; and now to create and destroy new human lives through In-Vitro Fertilization and cloning? Dr. Peter Kreeft–Professor of Philosophy at Boston College–argues that Nietzche is the most destructive philosopher in history. This form of Nietzchean arrogance–pride– fails to recognize the proper relationship between creature and Creator. Man does not define truth; rather, he discovers Truth–God–as existing objectively outside of his own being. The German philosopher Martin Heidegger (1889-1976)–founder of existentialism– remarked that thoughtlessness is an uncanny guest who comes and goes everywhere in today’s world. Many people live on the surface of existence. They have been seduced by immediate concerns and are almost unable to seek transcendent meaning. These persons, Heidegger argued, have fallen from human authenticity. Life is characterized by idle talk, by a passionate curiosity about novelties, and by ambiguity–the appearance that everything is genuinely understood, though ultimately nothing is understood. Professor Charles Rice–Professor of Law at Notre Dame Law School– refers to a lecture given by Alexander Solzhenitsyn at Templeton University in 1983:
“Over half a century ago, while still a child, I recall hearing a number of older people offer the following explanation for the great disasters that had befallen Russia: Men have forgotten God; that’s why all this has happened.’ If I were called upon to identify the principal trait of the entire twentieth century, here too, I would be unable to find anything more precise and pithy than to repeat once again: Men have forgotten God.” (Rice, 4).
The Pontifical Academy of Scientists consists of some of the most eminent scientists throughout the world who are appointed by the Pope himself, John Paul II. The founder of this Academy, at the request of Pope John Paul II, was Professor Jerome LeJeune, MD, Ph.D., Professor of Fundamental Genetics at the Rene Descartes University of Paris Faculty of Medicine. Professor LeJeune discovered Trisomy-21 or Down’s Syndrome. The task of the Pontifical Academy of Scientists is to study scientific matters and render expert opinions scientifically in order that appropriate moral judgments can be formulated based upon authentic and accurate conclusions which are drawn from science. The Pontifical Academy of Scientists noted that the most urgent need now seems to be that of reestablishing the harmony between the demands of scientific research and indispensable human values.
because In-Vitro Fertilization (IVF)
In-Vitro fertilization involves the fertilization of an ovum by a spermatozoon in a test tube. The resulting cell formed–the zygote–possesses the full chromosome complement of forty-six chromosomes and starts undergoing cell division by mitosis. Modern biological science knows today that a new, human life that is both individual and unique begins at the moment of conception. The eminent geneticist, Professor Jerome LeJeune, M.D., Ph.D., at the Rene Descartes University of Paris Faculty of Medicine states: “Each human has a unique beginning which occurs at the moment of conception. A unique personal constitution is spelled out for the specific human being created whose personal constitution has not occurred before and will never occur again. The zygote is the most specialized cell under the sun in that no other cell will ever have the same instructions in the life of the individual being created. As the cell develops, nothing new is learned, but progressively a lot of things are forgotten. In other words, the information is written in the first cell and it is not written progressively in the other cells. The new findings prove differentiation and from the very beginning there exists an embryo. As soon as he has been conceived, a man is a man.” I concur with the Australian philosopher and bioethicist Nicholas Tonti-Filippini who is member of the Pontifical Academy of Scientists when he states: “A human life comes into existence when a soul gives form to matter and matter assumes the bodily identity of a being which is organized as a single, individual oriented toward the development of specifically human functions such as wondering, doubting, affirming, loving, etc. That life is entirely dependent upon the continued dynamic interaction between matter and form.” In other words, it would not be possible, even at the one-cell developmental stage called the zygote, for matter to become intrinsically organized without the presence of a soul. The technology of IVF takes the new human embryo and transfers the embryo (ET) to the uterus with the hope that there will be successful implantation. If the gametes (sperm and eggs) are both obtained from within the marriage, the IVF is said to be homologous. If either the sperm or eggs are obtained from a third party outside of the marriage, the IVF is said to be heterologous. Since heterologous IVF employs gametes from a third party outside of the marriage, there is a violation of the agreement of the spouses in marriage to become parents in and through each other alone. The procedure of IVF creates numerous “extra” embryos with the probable if not certain knowledge that some will be destroyed; some will be subjected to scientific experimentation and manipulation; others may be frozen in liquid Nitrogen at negative three-hundred degrees Celsius which is called cryopreservation. Recent studies published in the New England Journal of Medicine demonstrated that when more then four eggs were fertilized but only the two most robust looking embryos were chosen, pregnancy resulted at the same rate as when women received three or more embryos. Dr. Allan Templeton–Professor of Obstetrics & Gynecology at Aberdeen University–argues that fertilizing a greater number of eggs enables doctors to have more selectivity and pick the best embryos which “look nice and round and are dividing at a good rate.” It is obvious that IVF involves not only creating new human lives but selecting which ones will be allowed or preferred to live–this type of eugenics is nothing less than abortion. Success rates resulting in live births from IVF have been very disappointing. The American Fertility Association shows an overall success rate in terms of live births at 5.6%. Other clinics have reported a success rate of 9% leading to live births. Some clinics have claimed a success rate of 25% leading to live births. It is clear, therefore, that from a scientific perspective alone there has been a very poor success rate with IVF as a technology leading to live birth. (DeMarco, 123-24).
A Moral Analysis of In-Vitro Fertilization
IVF is a violation against the Natural Moral Law because the procedure itself disassociates the unitive from the procreative aspects of sexual relations. The Natural Law maintains that each new human life has two moral rights:
- To be directly conceived in utero from sexual intercourse in the context of marriage
- To undergo the period of nine months gestation in the uterus of the biological mother
Surrogate parenting results when a woman agrees to “gestate an embryo in her uterus for nine months” after which she has agreed to give up the child at birth. Despite the subjectively noble intentions of a surrogate mother desiring to help others overcome fertility problems they are having, surrogate parenting reduces women to objects who function as mere “biological incubators.” This exploits women by using them as an object. Furthermore, the child’s right to be conceived and born directly as a result of his parent’s actions and love is violated. Early on, we could see that IVF had led to the confusion of parenting in that one child could in principle have five parents: a sperm donor, an egg donor, a surrogate mother whose uterus is used for nine months of gestation, and a married couple who adopt the child legally. In fact, cases such as this have been litigated in court to establish who the parents are and who has a “right” to the child. In one such case, the surrogate mother claimed that even though the child she gestated for nine months was genetically not hers and even though she had signed a legal agreement to give up the child at birth, she could not give the child up because maternal-fetal bonding had occurred. IVF and surrogate parenting assault the dignity of the child because of the failure to recognize that no one–not even the parents– have a moral right to a child. Even within the context of marriage, a new human life must be seen as a gift given freely from God. It is frequently asked that if the technology of IVF could be perfected such that only one human embryo was created and was not subjected to disproportionate risks or harm if IVF would then be morally acceptable. The answer is negative because of the disassociation between the unitive and procreative aspects of conjugal intercourse, which reflect a violation of the Natural Law. This results in a violation of the child’s right to be conceived and born from his own mother in the context of marriage. It is the “means” used to accomplish the “end” which lead to a moral rejection of all types of IVF.
The Biology of Mammalian Cloning
Recently a college student in pre-medicine asked a question: If a human white blood cell (lymphocyte) has the exact DNA as does a zygote (the cell resulting from the fertilization of an ovum by a sperm), then why is it wrong to destroy a zygote yet not a lymphocyte? This question brings out the reality of what a clone is expected to be: A cell that should be genetically identical (DNA/genes)–apart from possible mutations– from the cell from which it was obtained. The metaphysical difference between a lymphocyte and a zygote is rooted in the fact that the lymphocyte does not by nature have the potential as does the zygote to develop into a complete human being. While there are various scientific methodologies which can be used to create a clone, we will examine Somatic Nuclear Cell Transplantation which is the procedure that was used to create the cloned sheep, Dolly. This procedure was used by Scottish scientists Ian Wilmut and K.H.S. Campbell and their team at Edinburgh’s Roslin Institute.
- Mammary gland cells were isolated from a mature sheep of the Fin Dorset breed. These cells are said to be diploid (2N) meaning that they contain twice the number of chromosomes found in gametes (sperm and egg cells). These mammary gland cells were grown in vitro (in a laboratory dish) to which nutrient factors were added that stimulated cell growth and cell division.
- The mammary gland cells were then deprived of nutrient growth factors which caused the cells to leave the cell cycle and enter the G phase which is a quiescent or “suspended” phase of the cell cycle. In this quiescent phase of the cell cycle, there is only one DNA molecule per chromosome.
- The Scottish ewe was then injected with hormones that stimulate ovulation. Oocytes (eggs) were produced from ovulation were collected and arrested during meiosis which is the cell division of gametes (sperm and egg cells) that results in chromosome reduction (1N) and genetic variation through crossing-over.
- A fine glass pipette was inserted into the egg cell and its nucleus (containing DNA) was removed.
- The egg cell was then placed next to the mammary gland cell. An electric shock was applied which temporarily disrupts the cell membranes causing the oocyte to fuse with the mammary gland cell. This resulted in the nucleus (DNA) of the mammary gland cell entering the egg cell. Factors present in the cytoplasm of the oocyte caused the mammary nucleus to again enter the cell cycle, synthesize DNA, and go through the various stages of mitosis. Over the next six days, the new embryo divided into a small ball of cells called a morula.
- Finally, Dr. Wilmut transferred the developing embryo into the uterus of a ewe.
- The birth of the lamb demonstrated that during the development of the mammary gland cell there was no irreversible modification of genetic information required for development to term.
A Moral Analysis of Human Cloning
We might begin by asking why there would be such interest in cloning. How could it be used to benefit humans? Answers commonly proposed include selection of healthy individuals free from genetic disorders; choice of sex (male or female) of offspring; creation of persons with unique talents; creation of the images of those who have died; creation of frozen embryos to be transferred in utero at a later date to provide spare organs thus sparing worry about immunological rejection that is often encountered today in organ transplantation. While these desires may appear virtuous, all moral actions must be analyzed by intention, means, and end result. If any of these three principles are not morally correct, the action is considered morally illicit. Our moral analysis will be restricted to the cloning of human beings since the same moral and ethical principles cannot be applied to human beings as applied to the lives of lower animals or plants. Human cloning–like IVF–creates new human life outside of the body thereby causing a rupture between the unitive and procreative aspects of sexual relations. This represents, therefore, a violation of the Natural Law and fails to recognize that a child is a free gift from God–nobody (including the parents) has a moral “right” to a child. The nature of conjugal intimacy suggests that each child has the right to be conceived as a direct result of his parents’ actions rooted in the context of marriage. Failure to acknowledge this and show unconditional respect for this automatically sets the foundation for the child to be rendered an “object” which can be subjected to manipulation as in selection of desired “healthy clones only,” non-therapeutic experimentation, or cryopreservation where human embryos are frozen in liquid Nitrogen at -300 degrees Celsius and later unfrozen for subsequent use. Cloning–like IVF–creates human life outside of the body and subsequently transfers the embryo (ET) to a uterus for implantation. One should note that the cloned sheep, Dolly, resulted after 277 oocyte-donor nucleus fusions. Only eight of the 277 started to develop as embryos and only one of the eight embryos reached birth: Dolly. It is obvious, therefore, that cloning also creates “extra” human embryos with the knowledge that some will be destroyed in the process and with the hope that at least one will survive embryonic transfer to the uterus and result in a live birth.
The Pontifical Academy of Scientists recently issued a report to John Paul II dealing with various aspects of human cloning. The Academy argues that human cloning represents a cruel, exploitative way of treating human beings even in early embryonic development. Also being proposed at this time and in fact operative at the federal level of the United States Government is the “clone-and-kill” option. This procedure allows the creation of human embryos but does not allow them to be transferred to the uterus for implantation; rather, these living human embryos are subjected to scientific observation, experimentation, and manipulation. There is, in fact, only one possible fate for such living human embryos: death. Those of us who serve on the American Bioethics Advisory Commission issued a report, Ban Human Cloning: Report of the American Bioethics Advisory Commission to the President of the United States where we asked President Clinton to establish a federal moratorium on all human cloning and to reject the “clone-and-kill” option. How atypical is the reality today that with human cloning a woman can be the twin sister of her mother, lack a biological father, and be the daughter of her grandmother. The human cloning process perverts the basic relationships of the human person: filiation, consanguinity, kinship, and parenthood. The Pontifical Academy of Scientists noted to John Paul II that while IVF has already confused parentage, human cloning will mean the radical rupture of these bonds. Human beings come to depend not on their personal identity but rather on specific biological qualities that can be appraised and selected. This type of eugenics exploits the unique human individual into nothing more than ” a commodity for sale.” Halting the human cloning project, therefore, is a moral duty that must be translated into cultural, social, and legislative terms. The Academy recognizes that human cloning violates the principles of parity and nondiscrimination, allowing man’s domination over man and the discrimination which comes about through the whole selective-eugenic dimension inherent in this process. How paradoxical that Nietzche’s proclamation of the “death of God in the vain hope of a “superman” produces an unmistakable result: the death of man. (The Pontifical Academy for Life, 27-32).
The Current Status of the Human Genome Project
The Human Genome Project (HGP) is a worldwide project which will “map” or identify the physical location of the 100,000 human genes located on human chromosomes. Humans normally have 46 chromosomes. Forty-four are called autosomes and occur in pairs or homologues: one maternal, one paternal. The remaining 2 chromosomes are sex chromosomes and specify either a male (XY) or a female (XX). To study chromosomes–cells such as these lung fibroblasts–are grown in tissue culture in the laboratory and stimulated to undergo mitosis. Chromosomes are arrested during cell division and one obtains a chromosome spread as shown in this slide. The chromosomes are then arranged in pairs (maternal and paternal homologues) using various criteria so that a karyotype analysis is constructed as shown in this slide. Various banding patterns can be used to construct a karyotype as shown here. This slide demonstrates a normal karyotype consisting of 22 autosomes and the XY chromosomes indicating a male. The term genome refers to the entire set of instructions (3 billion bits) resting within the DNA that governs the production of proteins which are essential to normal cellular and physiologic activity. Scientific efforts will result in the construction of 3 separate types of genome maps:
- Genetic maps which delineate the linear order of genes on a chromosome;
- Physical maps which identify which genes are located on which chromosomes;
- Sequential maps which specify the DNA nucleotide sequence of a particular gene.
Only the sequential maps remain to be completed and it is estimated that completion will occur by the year 2005. Why is it so critical to know the sequencing of genes? It allows science to predict certain diseases with accuracy and efficiency. It is estimated that each of us has 5-50 genetic errors in our own genetic make-up although errors do not necessarily result in disease. It is important to remember that each of us is a product of interaction between our genes and our environment. The philosophy which asserts that “genes are destiny” is simply false (Furton, 3-4). Since genes are located on chromosomes at particular “loci,” let’s examine each of the 22 autosomes as well as the “X” and “Y” chromosomes and see some of the genes which have been mapped and their corresponding functions.
Chromosome 1:
The gene GBA is associated with Gaucher disease which results in a defective enzyme that is unable to metabolize glucocerebrosides (sugars) resulting in distended phagocytic cells.
The gene AD4 is associated with a form of Alzheimer’s Disease.
Chromosome 2:
The gene PAX3 is associated with Waardenburg Syndrome which causes deafness and changes in pigmentation.
Chromosome 3:
The gene SCLC1 when deleted is associated with one type of lung cancer.
Chromosome 4:
The gene HD results in Huntington’s Disease.
Chromosome 5:
The gene DTD when mutated results in diastrophic dysplasia.
Chromosome 6:
The gene IDDM1 is associated with juvenile onset diabetes where the body’s own white blood cells (T-lymphocytes) infiltrate and destroy insulin-producing pancreatic islet cells. This gene is associated with the Major Histocompatibility Complex (MHC).
Chromosome 7:
The CFTR gene encodes a chloride ion channel that is defective in patients with Cystic Fibrosis.
Chromosome 8:
The gene MYC is associated with Burkitt lymphoma which is a malignancy of white blood cells called B-lymphocytes. It is due to a reciprocal translocation between chromosomes 8 and 14.
Chromosome 9:
Malignant melanoma (an aggressive skin cancer) is associated with a mutation of a tumor suppressor gene CDKN2 which regulates cell cycle control.
Chromosome 10:
The gene MEN2A is associated with a syndrome of multiple endocrine neoplasia (type 2A) as is characterized by tumors in the thyroid, parathyroid, and adrenal glands.
Chromosome 11:
The gene LQT1 is associated with an inherited cardiac arrhythmia associated with mutations in an ion channel protein.
Chromosome 12:
The gene PAH is associated with a deficiency of the enzyme phenylalanine hydroxylase resulting in a disease called phenylketonuria (PKU). You may recall that many newborn infants often have their heels stuck to obtain a blood sample to screen for PKU.
Chromosome 13:
The gene BRCA2 is associated with a form of breast cancer.
The gene RB1 is associated with a childhood tumor of the retina called a retinoblastoma.
Chromosome 14:
The gene AD3 is associated with a form of Alzheimer’s Disease.
Chromosome 15:
The gene FBN1 is associated with Marfan Syndrome which is a generalized disorder of connective tissue.
Chromosome 16:
The gene PKD1 is associated with adult polycystic kidney disease characterized by large cysts. Patients with this disorder may die from renal failure or consequences of hypertension.
Chromosome 17:
The gene BRCA1 is associated with early-onset breast and ovarian cancer.
Chromosome 18:
Loss of the gene DPC4 causes pancreatic cancers to grow aggressively, as seen by tumor cells invading a nerve bundle.
Chromosome 19:
Atherosclerotic coronary artery disease is associated with the gene APOE that encodes apolipo-protein E, a ligand for the Low Density Lipoprotein (LDL) receptor.
Chromosome 20:
Severe Combined Immunodeficiency Disorder (SCID) which results in a gross functional impairment of immunity in regard to both T cells and B cells is due to a missing enzyme adenosine de-aminase which is associated with the ADA gene.
Chromosome 21:
The gene SOD1 is associated with Amyotrophic lateral sclerosis (Lou Gehrig’s Disease) due to a deficiency of the enzyme superoxide dismutase.
Chromosome 22:
Deletion of the gene DGS is associated with DiGeorge Syndrome which is a T cell deficiency.
X Chromosome:
Defects in DMD gene (dystrophin) cause Duchenne muscular dystrophy which is a fatal progressive degeneration of muscle tissue.
The gene FMR1 is associated with Fragile X Syndrome due to unstable nucleotide repeats.
Y Chromosome:
The gene TDF results in Testis-determining factor which binds to DNA and regulates genes controlling the development of the testis.
Ethical Considerations of the Human Genome Project
Significant ethical concerns have been raised regarding the Human Genome Project as to how knowledge of a person’s DNA could be utilized. Some scientists have likened the construction of the genome sequencing map to the construction of the periodic table in the 19th century (Furton, p.3). John Paul II noted that the human genome project, in a way, is the last continent to be explored. Due to the tremendous advances in the knowledge of genetics and molecular biology it is now possible to scientifically peer into the very inner fabric of life and the mechanisms that characterize individuals which ensure the continuity of living species. The Fourth General Assembly of the Pontifical Academy of Scientists examined as their focus, The Human Genome: Human Personhood and Future Society. One significant concern dealt with by the Academy is the relationship between knowledge obtained and power utilized. Knowledge of individual DNA sequences (genes) could lead to interference with the internal structure of human life whereby subduing, selecting, and manipulating the individual person and future generations occurs. We have already seen examples of this as exemplified by the destruction of living human embryos who were not of the desired sex or those embryos who carried defective genes. Such selective eugenics is based on a mistaken “quality of life” argument which is said to prevail over the sacredness of life. In fact, it is based on an erroneous anthropology. In addressing the Pontifical Academy of Scientists for Life, John Paul II recalled that anthropological reflection recognizes the substantial unity of body and spirit and that the human genome not only has a biological significance but an anthropological dignity which has its basis in the spiritual soul that pervades it and gives it life. It is already scientifically established that the inner truth of the genome is present at the moment of conception when the genetic inheritance of the father and mother are united, as Professor LeJeune from the University of Paris has noted. This correct anthropology of man leads to the recognition that the dignity of the human being as a person from the moment of conception must be guaranteed by civil law. The Church, therefore, makes an urgent appeal especially to political leaders and scientists to promote the good of the person through scientific research that perfects appropriate treatments which are therapeutic and without disproportionate risks to the human person. Many ask us today if prenatal tests such as amniocentesis, chorionic villus sampling (CVS), measurement of various fetal proteins found in amniotic fluid, or ultrasonography are morally acceptable. It is recognized that today there is a serious disproportion between diagnostic possibilities and therapeutic realities which can be carried out. Too often today empirical data obtained from prenatal diagnostic tests are being used to discriminate against those who demonstrate genetic/chromosomal abnormalities as exemplified by the destruction of living human embryos which is nothing other than direct abortion. It is morally unlawful, therefore, to carry out any procedure or intervention on the human genome unless it is aimed at the good of the person which is anthropologically understood as a unity of body and spirit. Nor is it morally lawful to discriminate between human subjects on the basis of possible genetic defects discovered before or after birth. We must emphasize direct support for families to welcome newborn life even when it suffers from serious defects or malformations. In John Paul II’s 1998 Address of the Fourth General Assembly of the Pontifical Academy of Scientists entitled, Dignity of the Human Genome, he made an urgent appeal especially to scientists to work in their research to promote scientific discoveries which are directed to the common good which can only be achieved through the good of each and every individual.
Reversal of Cystic Fibrosis Phenotype Using Gene Therapy:
An Ethical Technique
The Human Genome Project has allowed us the ability to not only locate, identify, and sequence genes located on particular chromosomes which are associated with particular disorders but also the possibility–indeed the reality–of correcting defective genes (DNA). Today, I will explore with you a mechanism of how this can be done using the disease cystic fibrosis as an example. Cystic fibrosis is a disease which is caused by the inheritance of 2 autosomal recessive genes–one from each parent or one maternal and one paternal. In humans, it causes pancreatic, pulmonary, and digestive dysfunction in children and young adults. Individuals with CF are subject to chronic pulmonary infections which can be life threatening and require intensive antibiotic therapy. Cystic fibrosis is the most common lethal autosomal recessive disease among Caucasians, with about 1 in 1,800 newborns having the disorder. Techniques in molecular biology have allowed us to sequence the DNA nucleotides of the CFTR gene that causes CF. The CFTR gene is a large gene containing 250,000 base pairs located on chromosome 7. The CFTR gene has been molecularly cloned. According to Dr. Bettina C. Hilman, MD, Professor of Pediatrics, Chief of Pulmonary-Allergy, Director of the Cystic Fibrosis Center for LSU School of Medicine, “At this time, there have been identified well over 700 mutations of the CFTR gene.”
A mouse model has been developed for CF to study the most common mutation, F508. In research published in The Lancet, researchers demonstrated at Umea University in Sweden how they successfully reversed the Cystic Fibrosis phenotype in mice by using gene therapy in utero. Knockout mice were created meaning that they exhibited the same abnormalities of the gastrointestinal tract as seen in human CF patients. Left untreated, these mice developed intestinal obstruction and 95% of them died as a result. Knockout fetuses at days 16-17 of gestation were infected with a virus as a vector carrying the normal CFTR gene. A vector is a means of getting a desired gene into a cell. Infection of the embryos was accomplished by injecting the viral vectors into individual amniotic sacs where the fetuses were developing. This procedure is somewhat analogous to performing amniocentesis at 15-20 weeks on human fetuses. The results were astonishing: the lethal Cystic Fibrosis phenotype in mice could be completely and permanently reversed by gene therapy involving the infection of knockout mice in utero with a viral vector carrying a normal CFTR gene. The authors concluded that this is the first demonstration of complete reversal of a mammalian lethal genetic disease by somatic-cell gene therapy.
The use of gene therapy in humans to reverse Cystic Fibrosis has also been studied. Dr. Francis S. Collins, MD, PhD is the Director for the National Center for Human Genome Research and acknowledges that CF has become the paradigm for the study of genetic diseases and for the medicine of the future. Dr. Collins goes on to say that it is possible to identify genes whose structure and function are unknown and to use that information to understand given diseases and develop ‘designer’ therapies which will become the central paradigm of biomedical research: Cystic Fibrosis is the disease that leads that charge. Dr. James Watson, MD, PhD is the Director of the Institute for Human Gene Therapy at the University of Pennsylvania in Philadelphia. Dr. Wilson states that 3 different vector systems for delivering the CFTR gene to CF airway cells have been used: Modified Adenovirus (AV), Adeno-associated virus (AAV), and microscopic fat capsules called liposomes. The goal is to get the normal CFTR gene into airway epithelial cells and to get the gene expressed without adverse consequences such as those which are immunological. Dr. Wilson brings out that three milestones have been achieved so far in the use of gene therapy in humans with CF:
- It has been shown that gene transfer is safe.
- There is evidence of successful gene transfer–getting the healthy genes into defective cells–and some indication that the gene turns on.
- In some cases, the genes are correcting the defective CF cells.
In using gene therapy to target the airway epithelial cells, questions arise concerning how much of the normal CFTR gene is needed to correct defective chloride transport. Some researchers (1996) have suggested that 5% of activity in every cell might be enough to correct the ion defect in a clinically meaningful way. Dr. Michael J. Welsh, MD at the University of Iowa College of Medicine has shown that correcting 10% to 20% or less of cells is enough to achieve nearly complete restoration of chloride transport. Areas of concern in gene therapy include the use of diferrent vectors to deliver the CFTR gene as well as ways to disarm the body’s immune system and to improve the amount of gene treatment that cells take in and to make the transfer process more efficient (Wilson, 1-7). Current research (1997) has demonstrated that it is possible to introduce the CFTR gene into airway epithelial cells of CF patients and that there has been evidence of expression at the molecular and functional levels (1997). Dr. Francis S. Collins, MD, PhD notes that clinical studies have progressed to the point at which vectors can be aerosolized to the entire lung. Dr. Collins is optimistic about the status of CF gene therapy in humans. Challenges to gene therapy include the number of airway epithelial cells needing to be exposed to a vector carrying the normal CFTR gene, ongoing expression of the CFTR gene, and immune responses when viral vectors are used.
Conclusion
I believe that there is no better synopsis of why we live today in a “culture of death” than that which is found in Evangelium Vitae. Choices once considered criminal by common moral sense are now becoming socially acceptable. What is both tragic and alarming is that certain sectors of the medical profession–who by nature are directed to defending and caring for human life–are increasingly willing to carry out actions against the human person and destroy life. This both distorts and contradicts the very nature of the medical profession; in fact, the dignity of those who practice such actions is degraded. Too often today conscience itself–darkened as it were by widespread conditioning–finds it difficult to distinguish between good and evil in what concerns the basic value of human life. The net result ends up with actions which poison and contaminate human society, harming those who practice such actions more than those who suffer from the injury. Moreover, they are a supreme dishonor to our Creator as John Paul II has stated in Evangelium Vitae. What are the root causes of such contradictions? It begins with a philosophy of subjectivism that is Nietzchean carried to an extreme where “freedom” and “autonomy” become absolute by the exaltation of the isolated individual. Freedom then negates and destroys itself and becomes a factor leading to the destruction of others when it no longer recognizes and respects its essential link with the truth that is objective. The absolutizing of the notion of freedom sets itself apart from all forms of tradition and authority, thereby denying an objective and universal truth which is the foundation of all personal and social life. The person is then left with no point of reference for his own choices about the truth of good and evil; rather, he has only his subjective, changeable opinion–his own egocentric interest and whim. This philosophical view of freedom leads to a serious distortion of life in society. People inevitably end up rejecting one another. This form of philosophical relativism leads to an ideology that everything is negotiable, everything is open to bargaining: even the first of the fundamental rights, the right to life. Christians–like all people of good will–are called upon under grave obligation of conscience not to cooperate formally in practices which, even if permitted by civil law, are contrary to the law of God. It is critical and urgent today that we foster the development of normal consciences which are properly sensitized and that we provide the appropriate support systems which allow people to live morally virtuous lives. John Paul II asked Professor Jerome LeJeune, MD, PhD to be the founder of the Pontifical Academy of Scientists for Life, in order that the Academy study and provide information and training about the principal problems of law and biomedicine pertaining to issues of life and especially those connected with moral theology and the directives of the Church’s Magesterium. This task is an ever ongoing one since biomedical science and technology are expanding at such a fast rate it is difficult for bioethics to keep pace.
There is a place for research–including cloning in the vegetable and animal kingdom–wherever it answers a need or provides significant benefit for man or other living beings as long as the rules for protecting the animal itself and the obligation to respect the biodiversity of species is observed. When scientific research in man’s interest aims to cure disease, relieve suffering or solve problems related to malnutrition, it represents a hope which God entrusted to humanity through the efforts and talents of scientists: “It is the outlook of those who see life in its deeper meaning, who grasp its utter gratuitouness, its beauty and its invitation to freedom and responsibility. It is the outlook of those who do not presume to take possession of reality but instead accept it as a gift, discovering in all things the reflection of the Creator and seeing in every person his living image.” (Evangelium Vitae, n. 83).
