HUMAN GENOME

A genome is an aspect of living organisms that enables them to pass on characteristics to the next generation. "Genome" specifies the totality of genes that make up the hereditary constitution of any particular organism. While each organism will have its own distinct set of genes (unless it is a twin), scientists seek to uncover the general attributes of the genomes of species as a whole. Thus, there are specialists studying the mouse genome, the frog genome, or the human genome. While this project lies within the field of organic science, much discussion has taken place over the social, ethical and economic implications of the study of the human genome. After giving a brief description of the Human Genome Project, this article will discuss the various issues raised, which can be grouped as follows: (1) marketplace issues, including ownership of genetic knowledge or materials, and patenting; (2) genetic discrimination, which leads to questions about privacy, about health insurance, life insurance, and employment; (3) genetic testing, both adult testing and pre-natal screening; (4) genetic counseling and its new challenges; (5) eugenics and the use of gene selection for trait enhancement rather than treatment of disease; (6) gene therapy, both somatic cell therapy and germline therapy; (7) theological principles and questions of free will, determinism, and "playing God" and (8) cloning and embryo research.

The Human Genome Project. The Human Genome Project has been the collaborative work of many scientists and laboratories in the United States seeking to chart the DNA of the human genome. The idea of coordinating genetic research first surfaced in 1985 and 1986 from several directions, involving both the U.S. Dept. of Energy and the National Institutes of Health. By 1990 the U.S. Congress had allocated 3 to 5 billion dollars to be spent over 15 years in the quest to "map" and "sequence" the human genome. Similar work has been undertaken in other countries, coordinated by an international group, the Human Genome Organization (HUGO).

As the scope and funding of this project has been vast, so has its goal. The proteins needed to keep a human person functioning are coded in approximately 30,000 genes. These genes make up the "words" of the code, using four different nucleotides. Each nucleotide contain a nitrogenous base (Adenine, Cytosine, Guanine, or Thymine) attached to an outer structure of sugar and phosphate. These nucleotides pair up along the spiraled double helix: A with T and G with C. It is estimated that the human genome contains three billion of these base pairs. If one considers each base pair as a single "letter," creating the code book for the human genome is equivalent to decoding 13 complete sets of the Encyclopedia Britannica. Furthermore, such a code book is only useful if a "grammar" is developed by which one can "read" what has been gathered. So this massive project involves both finding what is there, in terms of strings of nucleotides, and interpreting what it means.

While the HGP is publicly funded, other private industry groups have been seeking to map the human genome on their own. In June of 2000, a joint announcement was made by the National Institutes of Health and Celera Genomics, a private corporation in Maryland, claiming that the human genome had now been mapped. While these two endeavors have taken different research strategies, and while significant gaps in information still exist, the work of the two groups together constitutes a significant advance in the goal of identifying all the genetic markers on the human genome.

Selected Issues.

Ownership. In the United States, the rise of new technologies, as a necessary side-product of research, as well as new forms of genetic material (cloned strings of base-pair sequences) has stirred up a significant controversy over the patenting of genetic materials and processes. U.S. patent law was derived as an incentive for private industry to engage in research and development, but has long since recognized that natural materials cannot be patented. In other words, the U.S. Patent and Trademark Office has functionally recognized a distinction between inventions and discoveries, refusing to patent the latter. Work in genetics has challenged this easy distinction. For example, in 1991 a California company, Sy Stemix, applied for a patent on a composition of stem cells developed out of bone-marrow stem cells, a biological product that could be useful in treating leukemia or AIDS. Both the process of production and the stem cell composition were patented. Since the particular stem cell composition does not exist in human bodies on its own, this is deemed an invention rather than a discovery.

The patenting issue raises broader questions about the commodification of genetic knowledge. This became evident early on in the U.S. program, when one of the researchers from the National Institutes of Health sought a patent for the gene sequences he had identified. A controversy arose over whether NIH ought to seek patents, something that James Watson—co-discoverer of DNA and head of the HGP at the time—vehemently opposed on the grounds that such action would hamper the free flow of information, on which scientific collegiality depends. The controversy had several results: James Watson resigned as director of the HGP, while NIH withdrew its patent applications. The questions of (1) whether genetic knowledge involving so-called inventions can/should be patented and (2) whether such patents should be granted to government agencies (and whose names will appear on them) remain highly contested (see Peters, 1997, 126ff).

Another set of ownership questions arises in light of the Human Genome Diversity Project (Peters, 1998). While its goal is admirable, seeking—through regional centers around the world—to advance the study of genetic diversity (and thereby offset the assumption that the "normal" genome is that of a Western Caucasian), the ethical and legal problems have mounted quickly. The project depends on the collection of vast numbers of DNA samples from widely diverse populations. The question of ownership rights over these samples is complicated by the fact that the Western notion of informed consent assumes an individualism with little salience in non-Western cultures. Further, who will benefit from the

knowledge gained by such samples? Are we once again facing a situation in which aboriginal and Third World peoples are exploited, for access to their DNA, so that the more prosperous might benefit? Finally, how can we deal with the normative judgments that come with potential discoveries for example, if it were to be disclosed that the gene for schizophrenia is more prevalent in Native Americans than in other populations? Will the quest for diversity turn into another excuse for racism?

Genetic Discrimination. Once tests or treatments for a certain genetic condition are available (and some are), will this information will be used to segregate the "normal" from the "diseased"? Advances in treatment of such things as growth hormone deficiency, using genetically engineered techniques, raise fears that those living with certain congenital conditions will be pushed more and more to the margins. Those living with deafness, dwarfism, and other conditions, already vulnerable to social disdain, may be made to feel even more isolated. In sum, will new developments in the treatment of genetic conditions exacerbate prejudice with regard to certain disabilities?

Genetic Testing. With tests for adult onset diseases such as Huntingdon's Chorea now available, the possibility of genetic discrimination is real. Debates in this area

revolve around concerns for confidentiality, employment, and life and health insurance. With the growing ability to determine which individuals carry which disease genes, efforts to ensure genetic privacy are increasing. There is particular concern that genetic information, in the hands of insurers or employers, will lead to discriminatory practice.

The insurance industry will change dramatically once genetic disease testing becomes routine. There are two approaches to risk classification and health insurance: the libertarian approach assumes that persons should pay premiums according to their risk classification, while the egalitarian view assumes that the risk burden should be borne by all, regardless of the personal probability of illness. As the ability to predict health risks based on genetic tests grows, these two approaches will come into conflict. The entire insurance industry, founded as it is on actuarial tables and calculations of risk, will be challenged by new information about probabilities of future illness.

The possibility of being tested to see if one has a gene for a specific disease has been the most immediate practical result of the Human Genome Project. Yet the benefits of such testing are not so simple as they might seem. Not all genetic disorders arise from a single genetic mutation; some are multifactorial, meaning that they arise from the interaction of several genes, along with environmental factors. In these cases, as with breast cancer, heart disease, and diabetes, identifying genes simply indicates a propensity for a disease. Other cases are much more clear cut but nonetheless raise difficult questions. Huntingdon's disease is determined by a single genetic mutation: a person either does or does not have it, and one who does will get the disease. Having a relative who has had the disease is the indicator of risk. Whether an individual at risk wants to know for certain or not is a further question. In almost all cases, the technology for testing an individual's disease status has far outrun the development of treatments for a disease, putting many in the situation of having knowledge without effective options. Moreover, such genetic testing is almost never an individual matter: others who are at risk will be affected by the knowledge, either because they will be caretakers or because one person's status may have implications for their own. The potency of such genetic knowledge has led some to label this "toxic knowledge."

The genetic testing issues come to a head in the case of prenatal genetic testing. This can take the form of testing fetuses in the womb or of testing embryos in vitro, before implantation. The lack of effective treatment for most genetic diseases means that the point of genetic testing is simply to provide parents with the option of not having a certain child, either by abortion (in the case of fetal testing) or through discarding embryos before implantation. The Catholic position rejects both abortion and in vitro fertilization, raising the question of whether genetic screening (of all pregnant women) or genetic testing (of those shown to be at risk) is even desirable. Assumptions of "normality" versus "deformity," along with the presumption in favor of abortion for defective children, press the questions of genetic discrimination once again: to choose to have a child with a disability, even a fatal one, can put parents in a counter-cultural position.

Genetic Counseling. Genetic counseling is a relatively new profession, begun in order to explain genetic risks and probabilities to parents, usually those who already have one child suffering from a genetic disease. The rapid growth in genetic testing technology has created many new challenges for those in this profession. As genetic testing becomes more and more common, not only with regard to prospective parents but with persons tested for adult onset diseases, the engagement of the counselor in making normative judgments comes to the fore. Counselors are seeing the limitations of merely providing information, and are being pressed to help in decision-making and on-going support of families in crisis. The presumption of value neutrality on the part the genetic counselor is being questioned. Clergy and other pastoral counselors may have an important role to play in this area, though many, if not most, are poorly informed in basics of genetic medicine. Further, counselors themselves are raising concerns over genetic enhancement and the criteria for normalcy. What is the counselor to do, for example, if parents come seeking ways to ensure that they have a child who is tall, or bright, or, alternatively, deaf or dwarfed?

Eugenics. Another area of concern emerges: the question of eugenics and whether genetic technology ought to be used to engineer ideal traits in individuals or a more ideal population in general, or both. The notion that humans might enhance the gene pool through social policy and mating practices is an old one, with a very jaded history. Many discussions of genetic engineering move quickly to recounting the horrors of Nazi eugenic policies and the incipient racism of earlier eugenics movements. Nevertheless, dismissing eugenics as prejudicial requires further nuance with regard to the very category of "disease." Here the question is where and how to draw the line between genetic traits and genetic diseases, and which deserve medical treatment (Shinn 1996; Walters and Palmer 1997).

For example, if genetically altered hormones are available to help those with Growth Hormone Deficiency, what about their use in promoting tallness for those who wish it? If parents' hopes for their child include developing talents as a basketball player, why not use genetically engineered drugs to assist in this goal? These questions strike at the heart, not only of ideals about perfection and normality, but of the freedom of choice that grounds modern culture. If a couple wants to use genetic knowledge to enhance their child's biological makeup, and if they can afford to pay for the necessary procedures, what should prohibit them from doing so? Likewise, if parents want a child with certain characteristics, why not select among embryos screened for such characteristics in order to implant the desired ones in the mother's womb?

Such eugenics, whether based on individual choice or social policy, is rejected on several accounts from the Catholic perspective. First, modern genetics depends almost entirely on the conception of embryos outside the womb, in vitro, and the subsequent selective implantation of genetically preferred embryos in the mother. This technology was rejected by the encyclical Donum vitae in 1987 due to its violation of the marital act. Further, the commodification of children involved in such a eugenics mentality directly contradicts the Catholic notion that children are gifts, not products or achievements. Children, complete with their genetic assets and liabilities, are to be conceived through unitive marital acts and to be welcomed as gifts from God.

Genetic Therapy. Another complex result of the Human Genome Project lies in the area of genetic therapy. The first point to be made in this regard is the distinction between somatic cell therapy and germline therapy. Somatic cells include all the cells of the body, while germline cells are the reproductive cells, eggs and sperm as well as embryos. Gene therapy that targets somatic cells seeks to affect the symptoms of a disease, or alter the genetic composition of cells that are defective due to genetic disease. For example, cystic fibrosis arises from a defective gene that prevents liquid from being transported through cell membranes, resulting in mucous accumulation in the lungs. Attempts have been made to deliver aerosolized, normal genes to the lungs of affected patients in order to correct the deficiency. These kinds of treatments need to be repeated regularly and, even if the effectiveness of the technology improves dramatically, will have an impact only on the life of the individual patient. Germline therapy would involve altering the genes of the patient's egg or sperm (or an embryo conceived by the patient) so that his or her child would not be affected by the disease. What is distinctive about this latter kind of therapy, yet to be developed, is that it would have an impact on all future generations, not merely the affected individual (Walters and Palmer 1997).

Generally, the ethical concerns over somatic cell therapy remain simply those of any medical research: informed consent, assessment of risk, cost-benefit analysis, etc. These standard principles break down with germline therapy: the persons affected do not yet exist and cannot therefore provide informed consent, and the risks are hard to calculate since the effects of tampering with DNA may not appear for several generations. Further, the research itself cannot go forward without experimentation on human embryos. While those who do not hold that life begins at conception find such research not only acceptable but urgent, the Catholic insistence on the dignity of life from the moment of conception rejects all such research. Even if germline therapy could move beyond tampering with embryos in vitro (to altering ova and sperm), there still remains the concern over eugenics and discrimination: if we begin altering future generations in order to cure disease, what is to stop persons from using the same techniques to eliminate unwanted characteristics from the population? What will happen to the diversity of the gene pool?

Theological Principles. Implicit in many of the concerns about justice and social policy discussed above is the notion of the dignity of the human person and the preferential focus on the poor, the vulnerable, and the marginalized, including embryos. This applies to questions of global justice as well as issues of discrimination, access to health care, racist eugenics, and concerns for the unborn.

A related salient question with regard to the Human Genome Project has to do with theological anthropology and the divine. Just what does it mean to be human and how do new genetic knowledge and capabilities alter our view of the human-divine relationship? These questions have entered the literature as discussions of the "gene myth" and "playing God" (Peter 1997). Almost all Christian theologians reject any absolute genetic determinism, harkening to the theological notion of humans as created imago Dei —in the image of God—with rationality and free will. Yet the limit of this freedom is highlighted by the oft-repeated insistence that humans must not try to usurp the role of God. Still, this latter injunction raises its own problems, since not intervening at all in the natural order is an utter impossibility. How far human agents can go in altering processes at the level of DNA remains a hotly disputed question.

The two sides of this conundrum are evident in the different models to which theological ethicists appeal. Those more in favor of pressing the edges of genetic therapies emphasize the duty toward alleviating suffering, and insist on modeling this work after Jesus as a divine healer. Those who want to be more cautious about advances in genetic research and treatment tend to focus more on natural law and the dangers of human hubris. Both streams of thought are present in the Roman Catholic tradition, with its legacy of works of mercy and medical missions as well as its adherence to a natural law theory that cautions against excessive intervention in nature.

Cloning. While not a direct result of the HGP, cloning nevertheless has yielded great debate in the past several years. The birth of Dolly, the cloned sheep, at the Roslin Institute in Scotland in the spring of 1997 brought the possibility of human cloning to the fore. This event elicited a wide range of perspectives, ethically, theologically, and denominationally (Cole-Turner 1998). Those who oppose human cloning most strongly identify themselves with either the Reformed tradition or the Roman Catholic tradition. Their arguments focus on the uniqueness and divinity of each individual, the reductionism and consumerism inherent in most bio-technologies, the disruption of family integrity, and the hubris of genetic manipulation.

For those who are not entirely opposed to human cloning, several themes appear repeatedly. Many question whether human cloning is even possible, given the technological and moral obstacles. It took 277 tries before Dolly was born. Of these, only 29 embryos survived beyond six days and 62 percent of fetuses implanted in ewes were lost by 14 days. In other words, the wastage in terms of human embryos would be extreme, not to mention the number of women needed to undergo implantation and pregnancy, with little hope of bringing a baby to term. Many believe that these facts alone will set sanctions against proceeding towards human cloning. Others believe that the technology already exists, and it is only a matter of time before it reaches the public domain.

The point most often made by those cautiously accepting of human cloning is that this reproductive process, in and of itself, will not destroy the unique identity of an individual. Genetic makeup is only a portion of individual identity, as is illustrated in the case of identical twins.

Other ethical concerns focus on the motives for creating a clone. Given other available procedures for dealing with infertility, the reasons for wanting a clone come down to the following: (1) to clone oneself or to create children with enhanced genetic capabilities; (2) to create a second child genetically identical to a first child who is terminally ill, in order to aid in treatment of the ill child; or (3) to create a replacement for a child who has died. None of these seem to be warranted, on the grounds that each motive makes of the clone an instrument used in fulfilling another's aspirations or needs. Since there is no way to obtain informed consent from the clone for such an instrumental birth, human cloning is rendered suspect.

Bibliography: a. r. chapman, Unprecedented Choices: Religious Ethics at the Frontiers of Genetic Science (Minneapolis 1999). r. cole-turner, ed., Human Cloning: Religious Responses (Louisville 1997). m. junker-kenny and l. s. cahill, eds., The Ethics of Genetic Engineering (Maryknoll, NY 1998). j. f. kilner, r. d. pentz, and f. e. young, eds., Genetic Ethics: Do the Ends Justify the Genes? (Grand Rapids, MI 1997). t. peters, Playing God? Genetic Determinism and Human Freedom (New York 1997). t. peters, ed., Genetics: Issues of Social Justice (Cleveland 1998). r. l. shinn, The New Genetics (London 1996). l. walters and j.g. palmer, The Ethics of Human Gene Therapy (New York 1997). r. a. willer, ed., Genetic Testing and Screening: Critical Engagement at the Intersection of Faith and Science (Minneapolis 1998).

[c. s. w. crysdale]