Human Genome Project
Perspective (Genetics & Inherited Conditions)
April 25, 2003, was the fiftieth anniversary of the publication of the double helix model of DNA by James Watson and Francis Crick, based on the experimental data of Rosalind Franklin and others. It was fitting then, that fifty years later, in April of 2003, the complete sequence of the human genome was published, marking probably one of the greatest achievements not only in genetics but also in all of science. In the years since then, thousands of scientists are mining these data for information about the human body, how its genes shape development and behavior, and the role mutations play in diseases.
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Origins of the Human Genome Project (Genetics & Inherited Conditions)
The Human Genome Project (HGP) began as a result of the catastrophic events of World War II: the dropping of atomic bombs on the Japanese cities of Nagasaki and Hiroshima. There were many survivors who had been exposed to high levels of radiation, known to cause mutations. Such survivors were stigmatized by society and were considered poor marriage prospects, because of potential genetic damage. The U.S. Atomic Energy Commission of the U.S. Department of Energy (DOE) established the Atomic Bomb Casualty Commission in 1947 to assess mutations in such survivors. However, there were no suitable methods to measure these mutations, and it would be many years before suitable techniques would be developed. Knowing the sequence of the human genome would be the greatest tool for identifying human mutations.
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Advances in Molecular BiologyMolecular genetics (Genetics & Inherited Conditions)
As in all areas of science, progress in molecular biology was limited by available technology. Many advances in molecular biology made feasible the undertaking of the HGP. Starting in the 1970’s, techniques were developed to isolate and clone individual genes. By 1977, Walter Gilbert and Frederick Sanger had independently developed methods for sequencing DNA, and in 1977 Sanger’s group published the sequence of the first genome, the small bacterial virus Phi X174. In 1985, Kary Mullis and colleagues developed the method of polymerase chain reaction (PCR), in which extremely small amounts of DNA could be amplified billions of times, providing significant amounts of specific DNA for analysis. Finally, in 1986, Leroy Hood and Applied Biosystems developed an automated DNA sequencer that could sequence DNA hundreds of times faster than was previously possible. Additional advances in computer technology now made it possible to sequence the human genome.
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The “Holy Grail” of Molecular Biology (Genetics & Inherited Conditions)
In 1985 a conference of leading scientists was held at the University of California, Santa Cruz, to discuss the feasibility of sequencing the entire human genome. Biologists were looking for the equivalent of a Manhattan Project for biology. The Manhattan Project was the concerted effort of physicists to develop atomic weapons during World War II and resulted in huge increases of government funding for physics research. Walter Gilbert called the HGP the Holy Grail of molecular biology. With impetus from the DOE and the National Research Council, the Human Genome Project was launched in 1990 with James Watson as head. The goal of this project was to completely sequence the human genome of three billion base pairs by 2005 at a cost of $1.00 per base pair. In 1992, Watson resigned over a controversy surrounding the patenting of human sequences. Francis Collins took over as head of the HGP at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH). The sequencing of genetic model organisms, in addition to the human genome, was another of the goals of the NHGRI. This included genomes of the bacterium Escherichia coli, yeast, the fruit fly Drosophila melanogaster, the roundworm Caenorhabditis elegans, and other organisms. Moreover, 10 percent of the funding was to be directed toward studies of the social, ethical, and legal implications of...
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Competition Between the Public and Private Sectors (Genetics & Inherited Conditions)
Craig Venter, a former National Institutes of Health researcher, left the NIH and formed a private company, The Institute for Genomic Research (TIGR). TIGR, using a different approach (known as the shotgun method) was able to sequence the 1.8 million-base-pair genome of the first free-living organism, the bacterium Haemophilus influenzae, in less than a year. In 1998 Venter along with Perkin-Elmer Corporation formed the biotech company Celera Genomics to sequence the human genome privately. Celera had more than three hundred of the world’s fastest automated sequencers and a supercomputer to analyze data. Meanwhile, public funds supported scientists in the United States, the United Kingdom, Japan, Canada, Sweden, and fourteen other countries working on HGP sequencing. The public sector was now in competition with Celera. To assure free access, each day new sequence data from the public projects were made available on the Internet.
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The Human Genome Project Is Completed (Genetics & Inherited Conditions)
In 2001 the first draft of the human genome sequence was published in the February 15 issue of Nature and the February 16 issue of Science. There are many short, repeated sequences of DNA in the genome, and certain regions that were difficult to sequence that needed to be sequenced again for accuracy, plus proofreading the sequence for errors in the process. Thus in April, 2003, the final sequence of the human genome was achieved. It is remarkable that a government-funded project was completed two and a half years ahead of schedule and under budget, due to the ever increasing improvement of DNA technology and accuracy. April 25, 2003, was designated National DNA Day and has remained an annual day to educate the public, especially school-age children, about DNA and genetics in general.
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Findings from the Human Genome Project (Genetics & Inherited Conditions)
Perhaps the most surprising finding from the HGP is the relatively small number of human genes in the genome. Scientists had predicted the human genome would contain about 100,000 functional genes, yet the actual number of protein-coding sequences is approximately 25,000, representing only about 1 percent of the entire genome. In comparison, yeast has about 6,000 genes, the fruit fly about 13,000, and the Caenorhabditis about 18,000. It was surprising that a complex human had less than twice the number of genes as the roundworm. The human genome also contains 740 genes that encode stable RNAs. The genome of the mouse, another model genetic organism, is providing interesting comparisons to the human genome.
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Whose Genome Is It? (Genetics & Inherited Conditions)
Although more than 99.99 percent of the DNA sequences of all humans are identical, 0.01 percent difference equals approximately 30 million base pair changes among individuals. One important question is, then, whose genome was sequenced? Craig Venter has acknowledged that Celera has been sequencing mostly his DNA. However, the final sequence database is an “average” or “consensus” genome that is a conglomerate of many individuals contributing to the total sequence. Every human carries many and perhaps even hundreds of varying DNA changes. Even before the HGP was completed, databases listing single nucleotide polymorphisms were being established. These databases list the types of genetic variations that occur at individual nucleotides in the genome. For example, a cancer gene database lists the types of mutations that have been identified in specific cancer-causing genes and the frequency of such mutations. Mutations in genes such as BRCA1 and BRCA2 are responsible for breast and ovarian cancers, while mutations in the tumor-suppressor gene p53 have been found in the majority of human tumors.
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The Future: Genomics and Proteomics (Genetics & Inherited Conditions)
The Human Genome Project has given rise to two new fields of study. Genomics is the study of genomes. To do so requires databases and search engines to seek out information from these sequences. Today there are hundreds of such databases already established. Scientists can search for complete gene sequences if they know only a short segment of a gene. They can look for related sequences within the same genome or among different species. From such information one can study the evolution of particular genes.
The next step is to define the human proteome, giving rise to the field of proteomics. Proteomics seeks to determine the expression patterns of genes, the functions of the proteins produced, and the structure of specific proteins derived from their DNA sequence. If a particular protein is involved in a disease process, specific drugs to interfere with it may be designed. Humanity is just beginning to reap the benefits from the Human Genome Project.
Since 2003, many projects have developed to enhance our knowledge of the human genome. Two notable projects are the Human Cancer Genome Atlas Pilot Project and the Human Cancer Anatomy Project. The goals of both projects are to determine the genes that underlie the cause of more than two hundred known cancer diseases, to find targeted gene therapy treatments, and to prevent those diseases. To date, several outcomes have become important to further...
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Further Reading (Genetics & Inherited Conditions)
Collins, Francis, and Karin G. Jegalian. “Deciphering the Code of Life.” Scientific American 281, no. 6 (1999): 86-91. A description in lay terms of the progress and goals of the HGP.
Dennis, Carina, and Richard Gallagher. The Human Genome. London: Palgrave Macmillan, 2002. Written by two editors of the British journal Nature, the book gives a description of the HGP in lay terms and provides some of the information from the first draft of the human genome.
International Human Genome Sequencing Consortium. “Finishing the Eukaryotic Sequence of the Human Genome.” Nature 431 (2004): 931-945. The final draft of the Human Genome Project.
_______. “Initial Sequencing and Analysis of the Human Genome.” Nature 409 (2001): 860-921. The publication of the first draft of the Human Genome Project. The whole journal issue contains many other papers considering the structure, function, and evolution of the human genome.
Sulston, John, and Georgina Ferry. The Common Thread: A Story of Science, Politics, Ethics, and the Human Genome. Washington, D.C.: Joseph Henry Press, 2002. A chronicle of the race for the HGP from the perspective of British Nobel laureate Sir John Sulston, head of Sanger Centre, the British research unit involved in the HGP. Describes the effort to ensure public access to the genome data.
Wolfsberg, Tyra G., et al. “A User’s...
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Web Sites of Interest (Genetics & Inherited Conditions)
Department of Energy. Office of Science. http://doegenomes.org. Along with the National Human Genome Research Institute, conducted the Human Genome Project. Site includes discussion of the ethical, legal, and social issues surrounding the project, a genome glossary, and “Genetics 101.”
National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/Gene map99.. Starting with a general introduction to the human genome and the process of gene mapping, this site provides charts of the known genes on each chromosome, articles about the Genome Project and gene-related medical research, and links to other genome sites and databases.
National Human Genome Research Institute. http://www.genome.gov. One of the major gateways to the Human Genome Project, with a brief but thorough introduction to the project, fact sheets, multimedia education kits for teachers and students, a glossary, and links. Includes “Understanding the Human Genome Project,” an online education kit.
New York University/Bell Atlantic/Center for Advanced Technology. The Student Genome Project. http://www.cat.nyu.edu/sgp/parent.html. Uses interactive multimedia and three-dimensional technology to present tutorials and games related to the human genome and genetics for middle and high school students.
The Institute for Genomic Research...
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Human Genome Project (Encyclopedia of Genetic Disorders)
The Human Genome Project (HGP) is the international project to sequence the DNA of the human genome. The sequencing work is conducted in many laboratories around the world, but the majority of the work is being done by five institutions: the Whitehead Institute for Medical Research in Massachusetts (WIMR), the Baylor College of Medicine in Texas, the University of Washington, the Joint Genome Institute in California, and the Sanger Centre near Cambridge in the United Kingdom. Most of the funding for these centers is provided by the United States National Institute of Health and Department of Energy, and the Wellcome Trust, a charitable foundation in the UK.
Completely sequencing the human genome was first suggested at a conference in Alta, Utah in 1984. The conference was convened by the U.S. Department of Energy, which was concerned with measuring the mutation rate of human DNA when exposed to low-level radiation, similar to conditions after an attack by nuclear weapons. The technology to make such measurements did not exist at the time, and the sequence of the genome was one step required for this aim to become possible. The genome was estimated to be 3000Mb long, however, and sequencing it seemed an arduous task, especially using the sequencing technology of the time. If most of the DNA was "junk" (not coding for genes), then scientists assumed that they could speed the process along by...
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Human Genome Project (Encyclopedia of Science)
The Human Genome Project is the scientific research effort to construct a complete map of all of the genes carried in human chromosomes. The finished blueprint of human genetic information will serve as a basic reference for research in human biology and will provide insights into the genetic basis of human disease.
Fifteen-year federal project
The human "genome" is the word used to describe the complete collection of genes found in a single set of human chromosomes. It was in the early 1980s that medical and technical advances first suggested to biologists that a project was possible that would locate, identify, and find out what each of the 100,000 or so genes that make up the human body actually do. After investigations by two United States government agencieshe Department of Energy and the National Institutes of Healthhe U.S. Congress voted to support a fifteen-year project, and on October 1, 1990, the Human Genome Project officially began. It was to be coordinated with the existing related programs in several other countries. The project's official goals are to identify all of the approximately 50,000 genes in human deoxyribonucleic acid (DNA) and to determine the sequences of the 3.2 billion base pairs that make up human DNA. The project will also store this information in databases, develop tools for data analysis, and address any ethical, legal, and social...
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Human Genome Project (Encyclopedia of Public Health)
The Human Genome Project (HGP) is an international research program that aims to spell out the complete genetic inheritance of human beings and selected experimental animals. The HGP's goal is to decode the complete DNA inheritance, or genome, of human beings by 2003; following completion of a draft in 2000 that charted 90 percent of the human DNA inheritance. In addition to decoding human and animal DNA, the HGP trains scientists, develops techniques for analyzing genomes, and examines the ethical, legal, and social implications of human genetics research.
DNA is the long thread of a molecule that carries genes. Each strand of DNA, packaged as a chromosome, bears thousands of genes. Each gene contains the instructions for making a single component of the body, usually a protein. The hereditary instructions embedded in DNA are written with a four-letter alphabet (A, G, C, and T). A single misspelling in the DNA code can lead to the production of a defective protein, which can cause disease.
Understanding the human genome, the complete set of genes, sheds light on how the human body works at the fundamental level of molecules. Genes orchestrate the many fantastic and elegant features of life, like the development of embryos, while variations in gene sequence influence each person's susceptibility to diseases, including common illnesses like cancer and heart disease. The HGP will ultimately answer a wide range of scientific and medical questions, including: How do cells work? How do complex organisms develop from single cells? How are living beings related to each other? How do diseases arise?
The HGP was officially launched in 1990, as a joint project of the U.S. government and international partners. It was established as a large-scale, coordinated research project, marshaling the collaborative effort of hundreds of researchers. Between 1990 and 2003, the HGP is expected to reveal the sequence of approximately 3 billion "letters" that make up human DNA to identify all of the approximately 100,000 genes in human DNA, and to make all this information accessible to anyone with access to the Internet. The tools the HGP has built, including increasingly detailed maps of the human genome, helped genetic researchers navigate the genome and discover scores of disease genes in the 1990s. By 2003, a 99.99 percentaccurate listing of the letters that make up the DNA in all the human chromosomes is expected; that readout of the human genome, along with catalogs showing how DNA sequences vary among individuals, will help scientists tease out the genetic basis for complex diseases like diabetes, Alzheimer's disease, cancer, and heart diseaseillnesses whose origins can be traced to the effects of multiple genes, as well as social and environmental factors.
By helping reveal the molecular foundations of disease, the HGP is expected by some to transform health care. Genetic technologies are becoming increasingly available. For example, genetic tests are being used to confirm diagnoses for some conditions, and to help define prognoses. Other tests predict the risk for future health problems. In time, more detailed understanding of the molecules involved in disease is expected to promote more rational drug design, making for increasingly precise, in some cases individualized, pharmacologic therapies that will minimize side effects or even avoid them altogether. Ultimately, understanding the molecular origins of disease may reveal ways of preventing many diseases entirely, perhaps by circumventing molecular glitches that can lead to illness or by repairing the altered molecules outright.
While genetic information and technology are likely to create great opportunities for promoting health and preventing disease, some risks are likely to accompany these powerful technologies. Genetic information can be misinterpreted or misused. As knowledge about individuals' genetic backgrounds becomes increasingly widespread, some insurers and employers may use predictions about future health to limit or deny access to health care or employment. Therefore, protecting the privacy of genetic information and preventing genetic discrimination will be crucial. To tap the full benefits of genetics, the medical profession and the public will need to become better equipped to evaluate the meaning of genetic information and to make decisions about the use of the new genetic technologies. At the same time, proper oversight will be necessary to ensure that gene tests and technologies are valid and reliable, sensitive, and specific, and used in appropriate situations.
Genetics, which was largely confined to research laboratories during the twentieth century, is expected to pervade everyday life in the twenty-first century. In the arena of public health, it may be used to access individuals' risks for health problems and to develop programs of preventive health care. Knowing their susceptibility to various health risks, individuals may be able to adopt a schedule of surveillance, perhaps take medications that will prevent health problems, and ideally become motivated to adopt lifestyle measures that will minimize their risks.
Most observers argue that the goal of public health genetics programs should be phenotypic preventionreventing the emergence of diseaseather than genotypic prevention which is trying to change the genes people inherit. To attempt to prevent the transmission of particular genetic traits to future generations as a public health measure would tread into eugenic territory. Instead, public health goals should be designed to forestall the clinical manifestations of genetic risks.
FRANCIS S. COLLINS
(SEE ALSO: Genes; Genetic Disorders; Genetics and Health; Medical Genetics)
Collins, F. S. (1999). "Shattuck Lecture: Medical and Societal Consequences of the Human Genome Project." The New England Journal of Medicine 341:287.
Collins, F. S.; Patrinos, A.; Jordan, E.; Chakravarti, A.; Gesteland, R.; Walters, L.; and the members of the DOE and NIH planning groups (1998). "New Goals for the U.S. Human Genome Project: 1998003." Science 282:68289.
Juengst, E. T. (1995). "'Prevention' and the Goals of Genetic Medicine." Human Gene Therapy 6:1595605.
Khoury, M.; Burke, W.; and Thomson, E., eds. (2000). Genetics and Public Health in the Twenty-First Century: Using Genetic Information to Improve Health and Prevent Disease. New York: Oxford University Press.
National Human Genome Research Institute site on the World Wide Web: http://www.nhgri.nih.gov.
Human Genome Project (Encyclopedia of Science and Religion)
The worldwide effort, originally named the Human Genome Initiative but later known as the Human Genome Project or HGP, began in 1987 and was celebrated as complete in 2001. When begun, HGP was dubbed "big science" comparable to placing human beings on the moon. It was international in scope, involving numerous laboratories and associations of scientists around the world and receiving public funding in the United States of $200 million per year with a scheduled fifteen year timeline. The U.S. Department of Energy (DOE) began funding the project in 1987, followed by the National Institutes of Health (NIH) in 1990.
History and goals
The scientific goal was to map the genes and sequence human DNA. Mapping would eventually reveal the position and spacing of the then predicted one hundred thousand genes in each of the human body's cells; sequencing would determine the order of the four base pairshe A (adenine), T (thymine), G (guanine), and C (cytosine) nucleotideshat compose the DNA molecule. The primary motive was that which drives all basic science, namely, the need to know. The secondary motive was perhaps even more important, namely, to identify the four thousand or so genes that were suspected to be responsible for inherited diseases and prepare the way for treatment through genetic therapy. This would benefit society, HGP architects thought, because a library of DNA knowledge would jump start medical research on many fronts. Many early prophecies found their fulfillment. Some did not.
What was not anticipated was the competition between the private sector and the public sector. J. Craig Venter (b. 1946) led the private sector effort. While on a grant from NIH, Venter applied for nearly three thousand patents on Expressed Sequence Tags (ESTs). The ESTs located genes but stopped short of identifying gene function. A furor developed when researchers working with government money applied for patents on data that merely reports knowledge of what already exists in naturenowledge of existing DNA sequencesnd this led to the 1992 resignation of James Watson (b. 1928) from the directorship of NIH's National Center for Human Genome Research (NCHGR). Watson, who along with Francis Crick (b. 1916) is famed for his discovery of the double helix structure of DNA, was the first to head the NCHGR
Venter then established The Institute for Genomic Research (TIGR) and began using Applied Biosystems automatic sequencers twenty-four hours per day to speed up nucleotide sequencing and the locating of ESTs. By 1998 Venter had established Celera Genomics with sequencing capacity fifty times greater than TIGR, and by June 17, 2000, he concluded a ninety percent complete account of the human genome. It was published in the February 16, 2001, issue of Science.
Francis Collins (b. 1950) took over NCHGR leadership from Watson and found himself driving the public sector effort, racing with Venter toward the mapping finish line. Collins drew twenty laboratories worldwide with hundreds of researchers into the International Human Genome Sequencing Consortium, which he directed from his Washington office. Collins repudiated patenting of raw genomic data and sought to place DNA data into the public domain as rapidly as possible so as to prevent private patenting. His philosophy was that the human genome is the common property of the whole human race. The public project finished almost simultaneously with the private, and the ninety percent complete Collins map appeared one day prior to Venter's on February 15, 2001, in Nature.
Human DNA, as it turns out, is largely junkhat is, 98.6 percent does not code for proteins. Half of the junk DNA consists of repeated sequences of various types, most of which are parasitic elements inherited from our distant evolutionary past. Only 1.1 percent to 1.4 percent constitute sequences that code for proteins that function as genes.
Of dramatic interest is the number of genes in the human genome. At the time of the announcement, Collins estimated there are 31,000 protein-encoding genes; he could actually list 22,000. Venter could provide a list of 26,000, to which he added an estimate of 10,000 additional possibilities. For round numbers, the estimate in 2001 stood at 30,000 human genes.
This is philosophically significant, because when the project began in 1987 the anticipated number of genes was 100,000. It was further assumed that human complexity was lodged in the number of genes: the greater the number of genes, the greater the complexity. So, confusion appeared when, nearing the completion of HGP, scientists could find only a third of the anticipated number. Confusion was enhanced when the human genome was compared to a yeast cell with 6,000 genes, a fly with 13,000 genes, a worm with 26,000 genes, and a rice cell with 50,000 genes. On the basis of the previous assumption, a grain of rice should be more complex than Albert Einstein.
With the near completion of HGP, no longer could human uniqueness, complexity, or even distinctiveness be lodged in the number of genes. Collins began to speculate that perhaps what is distinctively human could be found not in the genes themselves but in the multiple proteins and the complexity of protein production. Culturally, DNA began to lose some of its magic, some of its association with human essence.
The theology and ethics of HGP
At the outset, HGP scientists anticipated ethical and public policy concerns; they were acutely aware that their research would have an impact on society and were willing to share responsibility for it. When in 1987 James Watson counseled the U.S. Department of Health and Human Services to appropriate the funds for what would become HGP, he recommended that three percent of the budget be allotted to study the ethical, legal, and social implications of genome research. Watson insisted that society learn to use genetic information only in beneficial ways; if necessary, the government should pass laws at both the federal and state levels to prevent invasions of privacy and discrimination on genetic grounds. Moral controversy broke out repeatedly during the near decade and a half of research.
Religious responses to the advancing frontier of genetic knowledge emerge mainly from people's concern to relieve human suffering and employ science to improve human health and wellbeing. A statement prepared by the National Council of Churches under the leadership of Union Seminary ethicist Roger L. Shinn affirms that churches in the United States must be involved with genetic research and therapy. "The Christian churches understand themselves as communities dedicated to obeying the will of God through service to others. The churches have a particular concern for those who are hurt or whose faith has been shaken, as demonstrated by the long history of the churches in providing medical care .Moreover, the churches have a mission to prevent suffering as well as to alleviate it."
In 1990 the Center for Theology and the Natural Sciences (CTNS) at the Graduate Theological Union (GTU) in Berkeley, California, obtained one of the first grants offered by the Ethical, Legal, and Social Issues (ELSI) division of NCHGR. A team of molecular biologists, behavioral geneticists, theologians, and bioethicists monitored the first years of HGP research to articulate theological and ethical implications of the new knowledge. Many religious and ethical issues eventually became public policy concerns. These are adumbrated below.
Genetic discrimination. When Watson recommended the establishment of ELSI, the first public policy concern was what he called privacy, here called genetic discrimination. An anticipated and feared scenario took the following steps. As researchers identify and locate most if not all genes in the human genome that either condition or, in some cases, cause disease, the foreknowledge of an individual's genetic predisposition to expensive diseases could lead to loss of medical insurance and perhaps loss of employment opportunities. As HGP progressed, the gene for cystic fibrosis was found on chromosome seven, and Huntington's chorea on chromosome four. Alzheimer's disease was sought on chromosome twenty-one, and colon cancer on chromosome two. Disposition to muscular dystrophy, sickle-cell anemia, Tay Sachs disease, certain cancers, and numerous other diseases turned out to have locatable genetic origins. More knowledge is yet to come. When it comes, it may be accompanied by an inexpensive method for testing the genome of each individual to see if he or she has any genes for any diseases. Screening for all genetic diseases may become routine for newborns just as testing for phenylketonuria (PKU) has been since the 1960s. A person's individual genome might become part of a data bank to which each person, as well as health care providers, would have future access. The advantage is clear: Medical care from birth to grave could be carefully planned to delay onset, appropriately treat, and perhaps even prevent or cure genetically-based diseases.
Despite the promise for advances in preventative health care, fear arises due to practices of commercial insurance. Insurance works by sharing risk. When risk is uncertain to all, then all can be asked to contribute equally to the insurance pool. Premiums can be equalized. Once the genetic disorders of individuals become known, however, this could justify higher premiums for those demonstrating greater risk. The greater the risk, the higher the premium. Insurance may even be denied those whose genes predict extended or expensive medical treatment.
Some ethicists are seeking protection from discrimination by invoking the principles of confidentiality and privacy. They argue that genetic testing should be voluntary and that the information contained in one's genome be controlled by the patient. This argument presumes that if information can be controlled, then the rights of the individual for employment, insurance, and medical care can be protected. There are grounds for thinking this approach will succeed. Title VII of the 1964 Civil Rights Act restricts pre-employment questioning about work-related health conditions. Paragraph 102.b.4 of the Act potentially protects coverage for the employee's spouse and children. Legislative proposals during the 1990s and early 2000s seem to favor privacy.
Other ethicists argue that privacy is a misguided cure for this problem. Privacy will fail, say its critics, because insurance carriers will press for legislation fairer to them, and eventually protection by privacy may slip. In addition, computer linkage makes it difficult to prevent the movement of data from hospital to insurance carrier and to anyone else bent on finding out. Most importantly, the privacy argument overlooks the principle that genome information should not finally be restricted. The more society knows, the better the health care planning can be. In the long run, what society needs is information without discrimination. The only way to obtain this is to restructure the employment-insurance-health care relationship. The current structure makes it profitable for employers and insurance carriers to discriminate against individuals with certain genetic configurationshat is, it is in their best financial interest to limit or even deny health care. A restructuring is called for so that it becomes profitable to deliver, not withhold, health care. To accomplish this the whole nation will have to become more egalitarianhat is, to think of the nation itself as a single community willing to care for its own constituents.
The Abortion controversy. Given the divisiveness of the abortion controversy in the United States and certain other countries, fears arise over possible genetic discrimination in the womb or even prior to the womb in the petri dish. Techniques have been developed to examine in vitro fertilized (IVF) eggs as early as the fourth cell division in order to identify so-called defective genes, such as the chromosomal structure of Down syndrome. Prospective parents may soon routinely fertilize a dozen or so eggs in the laboratory, screen for the preferred genetic make up, implant the desired zygote or zygotes, and discard the rest. What will be the status of the discarded embryos? Might they be considered abortions? By what criteria does one define "defective" when considering the future of a human being? Should prospective parents limit themselves to eliminating "defective" children, or should they go on to screen for enhancing genetic traits such as blue eyes or higher intelligence? If so, might this lead to a new form of eugenics, to selective breeding based upon personal preference and prevailing social values? What will become of human dignity in all this?
Relevant here is that the legal precedent set by Roe v. Wade (1973) would not serve to legitimate discarding preimplanted embryos. This Supreme Court case legalized the use of abortion to eliminate a fetus from a woman's body as an extension of a woman's right to determine what happens to her body. This would not apply to preimplanted embryos, however, because they are life forms outside the woman's body.
The Roman Catholic tradition has set strong precedents regarding the practice of abortion. The Second Vatican Council document Gaudium et spes (1965) states the position still held today: "from the moment of its conception life must be guarded with the greatest care, while abortion and infanticide are unspeakable crimes." The challenge to ethicists in the Roman Catholic tradition in the near future will be to examine what transpires at the preimplantation stage of the embryo to determine if the word abortion applies. If it does, this may lead to recommending that genetic screening be pushed back one step further, to the gamete stage prior to fertilization. The genetic make up of sperm and ovum separately could be screened, using acceptable gametes and discarding the unacceptable. The Catholic Health Association of the United States pushes back still further by recommending the development of techniques of gonadal cell therapy to make genetic corrections in the reproductive tissues of prospective parents long before conception takes placehat is, gametocyte therapy.
Genetic determinism, human freedom, and the gene myth. Religious thinkers must deal not only with laboratory science but with the cultural interpretations of science, as well as public policy influenced by both. A cultural myth has grown up with media coverage of the Human Genome Project that assumes "it's all in the genes." DNA has emerged as a cultural icon, holding the "blueprint" for humanity or being thought of as the "essence" of what makes a person a person. Even though molecular biologists withdraw from such extreme forms of genetic determinism, a cultural myth has arisen. Some commentators refer to it as the strong genetic principle; others call it the gene myth.
Genes, sin, crime, and racial discrimination. The belief in determinism promulgated by the gene myth raises the question of moral and legal culpability. Does a genetic disposition to antisocial behavior make a person guilty or innocent before the law? Over the next decade legal systems will have to face a rethinking of the philosophical planks on which concepts such as free will, guilt, innocence, and mitigating factors have been constructed. There is no question that research into the connection between genetic determinism and human behavior will continue and new discoveries will become immediately relevant to the prosecution and defense of those accused of crimes. The focus will be on the concept of free will, because the assumption of the Western philosophy coming down from Augustine that underlies understanding of law is that guilt can only be assigned to a human agent acting freely. The specter on the genetic horizon is that confirmable genetic dispositions to certain forms of behavior will constitute compulsion, and this will place a fork in the legal road: Either the courts declare the person with a genetic disposition to crime to be innocent and set him or her free, or the courts declare him or her so constitutionally impaired as to justify incarceration and isolation from the rest of society. The first fork would jeopardize the welfare of society; the second fork would violate individual rights.
That society needs to be protected from criminal behavior, and that such protection could be had by isolating individuals with certain genetic dispositions, leads to further questions regarding insanity and race. The issue of insanity arises because the genetic defense may rely upon precedents set by the insanity defense. The courts treat insanity with a focus on the insane person's inability to distinguish right from wrong when committing a crime. When a defendant is judged innocent on these grounds, he or she is incarcerated in a mental hospital until the medical evaluators judge that the individual is cured. Once cured, the person may be released. In principle, such a person might never be judged "cured" and may spend more time in isolation than the prison penalty prescribed for the crime, maybe even the rest of his or her life. Should the genetic defense tie itself to the insanity defense, and if one's DNA is thought to last a lifetime, then the trip to the hospital may become the equivalent of a life sentence. In this way the genetic defense may backfire.
With this prospect, we have returned to the specter of genetic discrimination. The current discussion of possible genetic influence on antisocial behavior is riddled with fears of discrimination, especially its racial overtones. Because the percentage of black men among the population of incarcerated prisoners is growing, society could invoke the gene myth to associate genes with criminal predispositions and with race. A stigma against black people could arise, a presumption that they are genetically predisposed to crime. University of California sociologist Troy Duster fears that if we identify crime with genes and then genes with race, we may inadvertently provide a biological support for prejudice and discrimination.
The gay gene. Theological and ethical debate has arisen over the 1993 discovery of a possible genetic disposition to male homosexuality. Dean H. Hamer and his research team at the U.S. National Cancer Institute announced that they discovered evidence that male homosexualityt least some male homosexualitys genetic. Constructing family trees in instances where two or more brothers are gay combined with actual laboratory testing of homosexual DNA, Hamer located a region near the end of the long arm of the X chromosome that likely contains a gene influencing sexual orientation. Because men receive an X chromosome from their mother and a Y from their father (women receive two X's, one from each parent), this means that the possible gay gene is inherited maternally. Mothers can pass on the gay gene without themselves or their daughters being homosexual. A parallel study of lesbian genetics is as yet incomplete; and the present study of gay men will certainly require replication and confirmation. Scientists do not yet have indisputable proof.
The ethical implications, should a biological basis for homosexuality be confirmed, could point in more than one direction. The scientific fact does not itself determine the direction of the ethical interpretation of that fact. The central ethical question is this: Does the genetic disposition toward homosexuality make the bearer of that gene innocent or guilty? Two answers are logically possible.
On the one hand, a homosexual man could claim that because he inherited the gay gene and did not choose a gay orientation by his own free will, he is innocent. The biological innocence position could be buttressed by an additional argument that homosexual activity is not itself sinful; it is simply one natural form of sexual expression among others. One could go still further to say that because it is biologically inherited that it is God's will; that a person's homosexual predisposition is God's gift.
On the other hand, one could follow the opposite road and identify the gay gene with a carnal disposition to sin. Society could claim that the body inherited by each person belongs to who they areeople are determined at least in part by what their parents bequeathed themnd that an inherited disposition to homosexual behavior is just like other innate dispositions such as lust or greed, which are shared with the human race generally; all this constitutes the state of original sin into which we are born. Signposts point in both ethical directions.
Beyond the question of guilt or innocence ethicists anticipate another issue, namely, the risk of stigma. Might the presence of the gay gene in an unborn fetus be considered a genetic defect and become grounds for abortion? Would routine genetic testing lead to a wholesale reduction of gay men in a manner parallel to that of children with Down Syndrome? Would this count as class discrimination?
Somatic therapy versus germline enhancement. The debate over two distinctionsomatic versus germline intervention and therapy versus enhancement interventionnvolves both secular and religious discussions. The term somatic therapy refers to the treatment of a disease in the body cells of a living individual by trying to repair an existing defect. The term germline therapy refers to intervention into the gametes, perhaps for the purpose of eliminating a gene such as that for cystic fibrosis so that it would not be passed along to future generations. Both somatic and germline therapies are conservative when compared to genetic enhancement. Enhancement goes beyond mere therapy for existing genes that may be a threat to health by selecting or adding genes to make an individual "superior" in some fashion. Enhancement might involve genetic engineering to increase bodily strength or intelligence or other socially desirable characteristics.
Ethical commentators almost universally agree that somatic therapy is morally desirable, and they look forward to the advances HGP will bring for expanding this important work. Yet they stop short of endorsing genetic selection and manipulation for the purposes of enhancing the quality of biological life for otherwise normal individuals or for the human race as a whole. New knowledge gained from HGP might locate genes that affect the brain's organization and structure so that careful engineering might lead to enhanced ability for abstract thinking or to other forms of physiological and mental improvement.
Religious ethicists argue that somatic therapy should be pursued, but enhancement through germline engineering raises cautions about protecting human dignity. In a 1982 study, the World Council of Churches stated: "Somatic cell therapy may provide a good; however, other issues are raised if it also brings about a change in germline cells. The introduction of genes into the germline is a permanent alteration .Nonetheless, changes in genes that avoid the occurrence of disease are not necessarily made illicit merely because those changes also alter the genetic inheritance of future generations .There is no absolute distinction between eliminating defects and improving heredity" (quoted in Peters, ed., 1998, pp. 6). The primary caution raised by the WCC here has to do with the lack of knowledge regarding the possible consequences of altering the human germline. The present generation lacks sufficient information regarding the long term consequences of a decision today that might turn out to be irreversible tomorrow. Thus, the WCC does not forbid forever germline therapy or even enhancement; rather, it cautions people to wait and see.
The Catholic Health Association is more positive: "Germline intervention is potentially the only means of treating genetic diseases that do their damage early in embryonic development, for which somatic cell therapy would be ineffective. Although still a long way off, developments in molecular genetics suggest that this is a goal toward which biomedicine could reasonably devote its efforts" (p. 19)
Another reason for caution regarding germline enhancement, especially among the Protestants, is the specter of eugenics. The word eugenics connotes the ghastly racial policies of Nazism, and this accounts for much of today's mistrust of genetic science in Germany and elsewhere. No one expects a resurrection of the Nazi nightmare; yet some critics fear a subtle form of eugenics slipping in the cultural back door. The growing power to control the design of living tissue will foster the emergence of the image of the "perfect child," and a new social value of perfection will begin to oppress all those who fall short.
Gene patenting. A controversy exploded in 1991 over gene patenting prompted by the filing for intellectual property rights by J. Craig Venter on nearly three thousand ESTs, expressed sequence tags. Each of these ESTs consisted of three hundred to five hundred base pairs made from cDNAs, copies of DNA sequences produced by polymerase chain reaction. ESTs are gene fragments, not whole genes; hence they mark the location of a gene but cannot identify gene function. Two issues became the focus of controversy. First, should the U.S. Patent and Trademark Office grant patents on genomic data? Even though the patents applied for were on copies of DNA sequences, their only value was to report raw genomic information. It appeared to critics that these applications failed to meet the three patenting criteria: novelty, utility, and nonobviousness. Second, should the U.S. government apply for and receive such patents in competition with the private sector? Venter's first patent applications were filed while he was working on a government grant; later he moved to the private sector and continued filing for intellectual property rights on his discoveries. James Watson followed by Francis Collins at the NIH both opposed patenting raw genomic data.
Cloning. Technically known as "somatic cell nuclear transfer," cloning techniques were developed in 1996 by Ian Wilmut at the Roslin Institute near Edinburgh, Scotland. Wilmut announced the cloning of Dolly the sheep in February 1997. The scientific breakthrough consisted of returning an already differentiated DNA nucleus to its pre-differentiated state and then transferring it to an ennucleated oocyte to make an embryo. The new embryo thus contains the genome of the donor nucleus. In the worldwide controversy that broke out in 1997 and continues in bioethical discussion, the debate seems to bypass the science of nuclear transfer; rather, the focus is on producing multiple human beings with duplicate genomes. Critics of reproductive cloning argue that children produced by cloning would suffer from loss of individuality, identity, and dignity. Roman Catholic critics along with Wilmut himself oppose human reproductive cloning on the grounds of safetyhat is, the imperfect technology would lead to the destruction of many early embryos. Defenders of nuclear transfer research distinguish sharply between reproductive cloning, which they oppose, and therapeutic cloning, which is necessary for stem cell research.
Stem cells. The isolation of human embryonic stem cells (hES cells) was accomplished in August 1997 by James Thomson at the University of Wisconsin on funds from the Geron Corporation. The hES cells are removed from the inner mass of the blastocyst, an embryo at four to six days old. When isolated and placed on a feeder tray, hES cells become immortalhat is, they divide indefinitely. In addition, they are pluripotent and able to differentiate into any and every tissue. The research goal is to control gene expression so as to make designated tissue for rejuvenating human organs. Some progress in gene control has been achieved. The next hurdle to jump is histocompatibility, namely, to avoid organ rejection by matching donor and recipient genetic codes. It is likely that experiments with somatic cell nuclear transfer will be required to attain histocompatibility. Ethical objections to stem cell research from Roman Catholics center on destruction of blastocysts for research purposes. Ethical support for stem cell research stresses beneficence; it emphasizes the marvelous advances in human health and wellbeing that this medical science might offer the human race.
Conclusion: theological commitments to human dignity
Virtually all Roman Catholics and Protestants who take up the challenge of the new genetic knowledge seem to agree on a handful of theological axioms. First, they affirm that God is the creator of the world and, further, that God's creative work is ongoing. God continues to create in and through natural genetic selection and even through human intervention in the natural processes. Second, the human race is created in God's image. In this context, the divine image in humanity is tied to creativity. God creates; so do human beings. With increasing frequency, humans are described by theologians as co-creators with God, making their human contribution to the evolutionary process. In order to avoid the arrogance of thinking that humans are equal to the God who created them in the first place, people must add the term created to make the phrase created co-creators. This emphasizes human dependency on God while pointing to human opportunity and responsibility. Third, these religious documents place a high value on human dignity.
By dignity they mean what eighteenth-century German philosopher Immanuel Kant meant, namely, that each human being is treated as an end, not merely as a means to some further end. As church leaders respond responsibly to new developments in HGP, one thing can be confidently forecast: This affirmation of dignity will become decisive for thinking through the ethical implications of genetic engineering. Promoting dignity is a way of drawing an ethical implication from what the theologian can safely say, namely, that God loves each human being regardless of his or her genetic makeup and, therefore, people should love one another according to this model.
See also BEHAVIORAL GENETICS; BIOTECHNOLOGY; CLONING; DNA; EUGENICS; FREEDOM; GENE PATENTING; GENE THERAPY; GENETIC DETERMINISM; GENETIC ENGINEERING; GENETICS; GENETIC TESTING; NATURE VERSUS NURTURE; PLAYING GOD; SIN; SOCIOBIOLOGY; STEM CELL RESEARCH
Catholic Health Association of the United States. Human Genetics: Ethical Issues in Genetic Testing, Counseling, and Therapy. St. Louis, Mo.: CHA, 1990
Chapman, Audrey R. Unprecedented Choices: Religious Ethics at the Frontiers of Genetic Science. Minneapolis, Minn.: Fortress, 1999
Coffey, Maureen P. "The Genetic Defense: Explanation or Excuse?" William and Mary Law Review 35, no.353 (1993): 352-396
Cole, David. "Genetic Predestination?" Dialog 33, no. 1 (1994): 20-21.
Cole-Turner, Ronald. The New Genesis: Theology and the Genetic Revolution. Louisville, Ky.: Westminster John Knox Press, 1993.
Cole-Turner, Ronald, ed. Human Cloning: Religious Responses. Louisville, Ky.: Westminster John Knox Press, 1997.
Cooke-Deegan, Robert. The Gene Wars: Science, Politics, and the Human Genome. New York: Norton, 1996.
Davies, Kevin. Cracking the Genome: Inside the Race to Unlock Human DNA. New York: Free Press, 2001
Duster, Troy. Backdoor to Eugenics. New York: Routledge, 1990
Eisenberg, Rebecca S. "Genes, Patents, and Product Development." Science 257 (992): 903-908
Genome Sequencing Consortium. "Initial Sequencing and Analysis of the Human Genome." Nature 409 (2001): 86021
Halley, Janet E. "Sexual Orientation and the Politics of Biology: A Critique of the Argument from Immutability." Stanford Law Review 46, no. 3 (1994): 503-568
Hamer, Dean H.; Hu, Stella; Magnuson, Victoria L.; et al. "A Linkage Between DNA Markers on the X Chromosome and Male Sexual Orientation." Science 261 (1993): 32127.
Holland, Suzanne; Lebacqz, Karen; and Zoloth, Laurie. The Human Embryonic Stem Cell Debate. Cambridge, Mass.: MIT Press, 2001.
Kevles, Daniel J., and Hood, Leroy, eds. Code of Codes: Scientific and Social Issues in the Human Genome Project. Cambridge, Mass.: Harvard University Press, 1992.
Lewontin, Richard C.; Rose, Steven; and Kamin, Leon J. Not In Our Genes: Biology, Ideology, and Human Nature. New York: Pantheon, 1984.
National Council of Churches. Human Life and the New Genetics. New York: Author, 1980.
Nelkin, Dorothy, and Lindee, M. Susan. The DNA Mystique: The Gene as a Cultural Icon. New York: W.H. Freeman and Company, 1995.
Paul VI. Gaudium et Spes. Pastoral Constitution on the Church in the Modern World (December 7, 1965). In Vatican Council II: Constitutions, Decrees, Declarations, ed. Flannery Austin. Northport, N.Y.: Costello: 1996.
Peters, Ted. Playing God? Genetic Determinism and Human Freedom. New York: Routledge, 1997.
Peters, Ted. For the Love of Children: Genetic Technology and the Future of the Family. Louisville, Ky.: Westminster John Knox, 1998.
Peters, Ted, ed. Genetics: Issues of Social Justice. Cleveland, Ohio: Pilgrim, 1998.
Reichenbach, Bruce R., and Anderson, V. Elving. On Behalf of God: A Christian Ethic for Biology. Grand Rapids, Mich.: Eerdmans, 1998.
Rifkin, Jeremy. Algeny. New York: Viking, 1983.
Shinn, Roger L. The New Genetics: Challenges for Science, Faith, and Politics. Wakefield, R.I. and London: Moyer Bell, 1996.
Venter, J. Craig, et al. "The Sequence of the Human Genome," Science 291 (2001):1304351.
World Council of Churches. Manipulating Life: Ethical Issues in Genetic Engineering. Geneva, Switzerland: Author, 1982