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The Human Genome Project: A Scientific and Ethical Overview

Marion L. Carroll and Jay Ciaffa

articlehighlights

Since the discovery of the double helix 50 years ago, DNA databases freely distribute information on the human genome but their use can lead to ethical issues, such as

  • germline engineering used solely for enhancement
  • the privacy of genetic information
  • mandatory genetic screening
  • genetic testing of newborns

August 2003

Scientific Background

The Human Genome Project hopes to improve lives by sequencing the genome.
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Francis Crick, one of the discoverers of the structure of the DNA molecule, lecturing ca. 1979. Source: Wellcome Library for the History and Understanding of Medicine. Photograph: Bradley Smith.

Scientists over decades have explored and mapped lands, oceans and the heavens with the expectation of increasing our awareness of the environment in which we live. Underlying this search for knowledge is also the desire to improve human existence through the discovery of beneficial resources. The Human Genome Project (HGP) has served to explore our genetic environment to make us aware of the beneficial resources that might contribute to understanding and improving our lives.9 The HGP involves the discovery and sequence of the full DNA complement in a single human somatic cell. Its primary goal is a listing and location of our genes — the single unit of heredity responsible for how we develop from conception, how we grow and mature, how we live, and how we die.

The discovery of the DNA double helix led to a new era of scientific research.

Dr. James Watson, one of the most well-known proponents of the Human Genome Project, contributed significantly along with Francis Crick, Rosalind Franklin and Maurice Wilkins to our understanding of the nature of DNA through the discovery of the structure of the DNA double helix.11 This discovery changed the focus of modern genetics and influenced the direction of many other disciplines in that the foundation of all life processes could now begin to be explored.12

Since then, technological advances have enabled scientists to study DNA and its structure in detail:

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DNA to be sequenced undergoes a lengthy process, using computer programs like this one to “read” DNA fragments. Source: DOE Joint Genome Institute.

Scientists have now determined the order of 98% of the 3-billion nucleotide base pairs of the human genome.
  • Computer generated analysis tools designed specifically to understand the significance of the base sequence in this large macromolecule have aided the Human Genome Project tremendously. These tools also aid in understanding how biochemical processes encoded in the sequence of bases are maintained, controlled, duplicated and terminated. With the development and modernization of the Fred Sanger dideoxy chain-terminating automatic sequencing method, the bacteria artificial chromosome (BAC) and the polymerase chain reaction (PCR), scientists have within 13 years been able to finish determining the order of 98% of the 3-billion nucleotide base pairs that compose the human genome.6 Simply knowing the sequence of bases at any given place or locus on a chromosome is not sufficient to understanding its function. As important as the sequence is to the function of genes, their distribution, location and structure among the 23 chromosome pairs is just as valuable when determining their role in different life processes. The estimate of between 30,000 and 40,000 genes is based on the fact that exons (gene segments) within the genome are flanked by known marker sequences (e.g., splice sites) that are located along the linear DNA sequence. Some computer programs can now recognize and label these segments and marker sequences while other programs can predict the location and structures of genes in genomic sequences from a variety of organisms. [Editor’s Note: See Computational Biology “learn more links” at end of this article.]
Genetics is now a key component in many other scientific fields.
DNA sequencing centers around the world work together to share information.
  • Through great effort and expense, scientists in molecular biology, biochemistry, math, computer science, engineering and the health care industry have worked together to turn what began in 1985 as a simple campus improvement project at the University of California, Santa Cruz into an international scientific consortium. This cooperative effort now known as the Human Genome Project, begun in 1989, was lead by the U.S. Department of Energy (DOE), formally the Atomic Energy Commission. The DOE was charged to investigate genetic mutations and genome structural integrity after observing the consequences of the development of the atomic bomb. Many universities, private industries and non-profit organizations from around the world have worked together to produce a complete reconstruction of the human genome for public display. The institutions involved in this consortium are often referred to as “sequencing centers.” These centers:3,7,10
  • offer facilities that allow scientists to determine the sequence of DNA of many different organisms including human
  • spend time and money in disseminating sequence information into publicly accessible databases
  • also develop computer programs that attempt to make biological sense out of the vast amount of sequence data being generated
The Internet has made it possible to gain instant access to DNA databases.
  • The accelerated development of the Internet is due in no small part to the need for communication between scientists at various DNA sequencing centers and to provide public accessibility to a DNA sequence database initially set up at the National Institutes of Health (NIH) at National Center for Biotechnology Information (NCBI). The database called GenBank is the major warehouse of genome sequence information from many different species and is accessible from many other web sites devoted to the utilization of sequence information.1,4
Technology accelerated the discovery of clues to heritable diseases and relationships among species.

April 25, 2003 marked 50 years since the publication in the journal Nature of the letter by James Watson and Francis Crick describing the DNA double helix structure. This day also marked the completion of the human genome sequence to 99.9% accuracy as announced by the National Human Genome Research Institute (NHGRI).8 In the wake of this enthusiasm for the completed project lies information that has only begun to provide science and medicine with clues to how to combat heritable diseases, how to improve medical applications, and how some of life’s seemingly most insignificant organisms like the fly, roundworm and mouse give us clues to better understand our natural selves.2,5,13,14 The door of discovery and knowledge has been opened and it is up to responsible individuals to use this information to improve our collective lives today and in the future.

Ethical Implications

The ethical issues raised by the human genome project can be grouped into two general categories: genetic engineering and genetic information.

Genetic manipulation for non-medical reasons can be an ethical dilemma.

Genetic engineering
The first category consists of issues pertaining to genetic manipulation or what is sometimes called “genetic engineering.” The map of the human genome provides information that will allow us to diagnose and eventually treat many diseases. This map will also enable us to determine the genetic basis of numerous physical and psychological traits, which raises the possibility of altering those traits through genetic intervention. Reflection on the ethical permissibility of genetic manipulation is typically structured around two relevant distinctions:

  • the distinction between somatic cell and germline intervention, and
  • the distinction between therapeutic and enhancement engineering

Somatic cell manipulation alters body cells, which means that resulting changes are limited to an individual. In contrast, germline manipulation alters reproductive cells, which means that changes are passed on to future generations. Therapeutic engineering occurs when genetic interventions are used to rectify diseases or deficiencies. In contrast, enhancement engineering attempts extend traits or capacities beyond their normal levels.

In germline engineering, changes are passed along in the genome of future generations.
  • The use of somatic cell interventions to treat disease is generally regarded as ethically acceptable, because such interventions are consistent with the purpose of medicine, and because risks are localized to a single patient.

  • Germline interventions involve more significant ethical concerns, because risks will extend across generations, magnifying the impact of unforeseen consequences. While these greater risks call for added caution, most ethicists would not object to the use of germline interventions for the treatment of serious disease if we reach the point where such interventions could be performed safely and effectively. Indeed, germline interventions would be a more efficient method for treating disease, since a single intervention would render both the patient and his or her progeny disease-free, thus removing the need for repeated somatic cell treatments across future generations.

Altering one gene may not achieve the desired enhancement since many traits involve a mix of genes.

Enhancement engineering is widely regarded as both scientifically and ethically problematic. From a scientific standpoint, it is unlikely that we will soon be able to enhance normally functioning genes without risking grave side effects. For example:

  • Enhancing an individual’s height beyond his or her naturally ordained level may inadvertently cause stress to other parts of the organism, such as the heart.
  • Moreover, many of the traits that might be targeted for enhancement (e.g., intelligence or memory) are genetically multifactorial, and have a strong environmental component. Thus, alteration of single genes would not likely achieve the desired outcome.
  • These problems are magnified, and additional problems arise, when we move from somatic cell enhancements to germline enhancements.
Future generations may feel limited by choices made regarding their genetic traits.

In addition to the problem of disseminating unforeseen consequences across generations, we are faced with questions about whether future generations would share their predecessors’ views about the desirability of the traits that have been bequeathed to them. Future generations are not likely to be ungrateful if we deprive them of genes associated with horrible diseases, but they may well feel limited by choices we have made regarding their physical, cognitive, or emotional traits. In short, there is a danger that social-historical trends and biases could place genetic limitations on future generations.

What rules should be set for the acquisition and use of genetic information?
Genetic screening results can create difficult situations for patients and their families.

Genetic information
The second general category consists of ethical questions pertaining to the acquisition and use of genetic information. Once we pinpoint the genetic basis for diseases and other phenotypic traits, what parameters should be set for the acquisition and use of genetic information? The key issue to be considered here is the use of genetic screening. Screening for diseases with the due consent of a patient or a legal proxy is generally viewed as ethically permissible, but even this form of screening can create some significant ethical challenges. Knowledge that one is or may be affected by a serious disease can create difficult situations for both patients and their families. Consider:

  • If a test is positive, what options, medical or otherwise, will be available to ameliorate the condition?
  • Will the patient’s relatives be informed that they too may be affected by the ailment?

It is the job of genetic counselors to educate patients about the implications of genetic knowledge, and to help patients anticipate and deal with these challenges.

Should mandatory genetic screening be rejected in all situations?

Mandatory genetic screening of the adult population raises serious ethical questions about personal liberty and privacy, and thus is not likely to garner widespread support. Nevertheless, we are likely to hear calls for mandatory genetic testing in specific social contexts, and existing practices will no doubt be cited as justifications for such testing. For example, in the justice system, longstanding practices of fingerprinting, urine testing, and blood testing are already being supplemented by DNA testing.

Genetic testing is of particular concern when it comes to health insurance.

Of particular concern is the specter of genetic testing in the insurance industry. When individuals apply for insurance policies, they are often required to provide family medical history, as well as blood and urine samples. At present, however, insurance companies in the United States cannot require genetic testing of applicants. While this prohibition is designed to prevent genetic discrimination, insurance industry lobbyists will surely be pressing the following kind of argument in coming years:

  • If it is considered fair and proper to identify applicants with high cholesterol and/or a family history of heart disease, and to charge those applicants higher premiums, why should it be considered unfair to utilize genetic testing to accomplish the same goals?
The genetic screening of newborns or others who are incapable of valid consent presents additional ethical questions.

Such questions will have to be seriously considered by ethicists and lawmakers, in the attempt to achieve a fair balance between individual rights and the rights of insurance companies. Indeed, the development of genetic screening for a broad array of diseases and conditions may eventually lead us to rethink the principles that are used to determine insurability and the apportionment of payment burdens.

Additional ethical questions arise when we consider genetic screening of newborns, young children, and others who cannot give valid consent for such procedures:

  • As more genetic tests become available, which ones should be universally administered to newborns?
  • What role should parental consent play in determining when children are screened?
Newborns are routinely tested for PKU without the explicit consent of parents.

Decisions about the implementation of universal genetic screening for newborns will likely follow existing policies, which perform tests for serious, early-onset diseases that are susceptible to treatment. The paradigm case for such universal screening is phenylketonuria (PKU). Newborns are routinely tested for PKU without the explicit consent of parents, under the assumption that parents want to know if their child is afflicted with this potentially devastating but easily treatable condition. Of course, the moral propriety of newborn screening becomes more complicated when we begin to deviate from this paradigm case. Determining whether screening should be pursued in cases like this will not always be easy:

  • What if the disease is not easily treatable, or can only be treated at great expense that parents may not want to incur?
  • What if an ailment is late onset and untreatable, as is the case with Huntington’s disease? What if a test can only determine a probability, not a certainty, that a child will develop a disease?
With genetic testing, there is potential for conflict between a parent’s choice and a child’s welfare.

Of course, from a legal standpoint parents have broad discretion when it comes to decisions about their children’s health and welfare, and this will no doubt hold true for decisions about both genetic testing and genetic engineering as these procedures become increasingly available. While this broad discretion is based on respect for parental autonomy and on a desire for minimal government intrusion into family life, we must acknowledge the potential for conflict between a parent’s choice and a child’s welfare.

  • What if a parent refuses to consent to a test that is clearly in their child’s best interest?
  • What if a parent decides to pursue a genetic “enhancement” that involves significant risks for a child, or that may limit a child’s life prospects?
Conclusion: As genetic engineering and information use increases, so will ethical questions.

While these questions may seem far-fetched to some, it is worth noting that current laws in most states allow parents to opt out of testing for PKU, despite the fact that this may leave their child exposed to a devastating disease.

Today, we face many important challenges pertaining to the use and distribution of genetic research and information. As our capabilities for genetic screening and genetic engineering increase, we are likely to encounter more difficult ethical questions, including questions about the limits of parental autonomy and the application of child welfare laws.

Marion Carroll, Ph.D., is an Assistant Professor in the Department of Chemistry at Xavier University of Louisiana teaching biochemistry, organic chemistry and genomics. He received his Ph.D. in Biochemistry from Louisiana State University Health Sciences Center in 2001. He engages undergraduate students in research that includes prostate cancer and the structure, function and distribution of short interspersed elements in primates. Dr. Carroll has published in Genomics, Genome Research and the Journal of Molecular Biology.
http://www.xula.edu/chemistry/profiles/mcarroll.php

Jay Ciaffa, Ph.D., is an Associate Professor of Philosophy at Xavier University of Louisiana. He received his Ph.D. in Philosophy from Tulane University in 1992. His publications include articles on Martin Heidegger and African-American Philosophy, and a book entitledMax Weber and the Problems of Value-free Social Science. His current research interests include biomedical ethics and critical social theory.
4/22/09, Update: Dr. Ciaffa no longer with Xavier University; he is now with Gonzaga University in Spokane, WA.
http://www.gonzaga.edu/Academics/Colleges-and-Schools/College-of-Arts-and-Sciences/Philosophy/faculty.asp

The Human Genome Project: A Scientific and Ethical Overview

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Discovery of DNA Structure and Function: Watson and Crick

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Kids Genetics

A fun, highly illustrated, site for kids with interactive elements about DNA, genes, heredity and more.
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The Human Genome Project: Overview

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Bioinformatics databases

A variety of tools and databases available from the EBI (European Bioinformatics Institute) and from sites belonging to its collaborators: Bibliographic Databases, Taxonomic Databases, Nucleotide Databases, Genomic Databases, Protein Databases, Microarray Databases. Also includes tutorials and other resources for educators.
http://www.ebi.ac.uk/2can/databases/index.html

Genetic Alliance

News, support groups, information on genetic conditions, as well as ethical, legal, and social issues. Also, a variety of ways to get involved (such as “action teams,” “advocacy groups,” and “e-mail discussion lists”) on its membership page.
http://www.geneticalliance.org/

Center on Medical Record Rights and Privacy

The Center on Medical Record Rights and Privacy is based at Georgetown University’s Health Policy Institute, a non-partisan multi-disciplinary group of faculty and staff dedicated to conducting research on key issues in health policy and health services research. The Center is dedicated to raising public awareness of the rights and responsibilities associated with medical records and other health information.
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Council for Responsible Genetics

Provides information on how to get involved in genetic issues and how to subscribe to CRG’s newsletter,GeneWatch.
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Teaching Resources from the Northwest Association for Biomedical Research (NWABR)

The Northwest Association for Biomedical Research (NWABR) strengthens public trust in research through education and dialogue. Its diverse membership spans academic, industry, non-profit research institutes, health care, and voluntary health organizations. Through membership and extensive education programs, it fosters a shared commitment to the ethical conduct of research and ensures the vitality of the life sciences community.

Ethics Primer
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Bioethics 101
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The Dolan DNA Learning Center

Timely information about genes in education, with a wealth of classroom resources.
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Computational biology resources

  • » The database called GenBank is the major warehouse of genome sequence. NCBI provides a link to GenBank and a user-friendly interface to genome information, sequencing data and bioinformatic tools that extract and manipulate sequence information to define the functional relevance of DNA sequences in research projects involved in discovering the foundation of many diseases and therapeutic interventions.
    http://www.ncbi.nlm.nih.gov/
  • » GENSCAN is a program used to predict the location and structures of genes in genomic sequences from a variety of organisms.
    http://genes.mit.edu/GENSCAN.html
  • » The bioinformatic tools for repetitive sequences like GRAIL, GENSCAN and this one called CENSOR are used to provide a way to answer the questions asked by anyone with Internet access about the role of a particular DNA sequence or sequences in protein structure, disease manifestation, genetic diversity, and drug interactions.
    http://www.girinst.org/Censor_Server-Data_Entry_Forms.html
  • » GeneCards® is an integrated database of human genes that includes automatically-mined genomic, proteomic and transcriptomic information, as well as orthologies, disease relationships, SNPs, gene expression, gene function and more.
    http://www.genecards.org/

Section: Scientific Background

  1. Benson, D.A., Boguski, M.S., Lipman, D.J. et al. “GenBank.” Nucleic Acids Research 27: 12-17, 1999.
  2. Comparative Mouse Genomics Centers Consortium: http://www.niehs.nih.gov/cmgcc/dbmouse.htm (accessed 8/10/03)
  3. DNA Data Bank of Japan: http://www.ddbj.nig.ac.jp/ (accessed 8/10/03)
  4. European Bioinformatics Institute: http://www.ebi.ac.uk/ (accessed 8/10/03)
  5. Flybase — A Database of the Drosophila Genome: http://flybase.bio.indiana.edu/ (accessed 8/10/03)
  6. Lander, E.S., Linton, L.M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., and the human genome consortium. “Initial sequencing and analysis of the human genome.” Nature 409: 860-921, 2001.
  7. Max Planck Institute for Molecular Genetics: http://www.molgen.mpg.de/ (accessed 8/10/03)
  8. National Center for Biotechnology Information: http://www.ncbi.nlm.nih.gov/ (accessed 8/10/03)
  9. National Human Genome Research Institute: http://www.genome.gov/ (accessed 8/10/03)
  10. Oak Ridge National Laboratory: http://www.ornl.gov/ (accessed 8/10/03)
  11. Watson James D. “The Human Genome Project: past, present and future.” Science 248: 44-51, 1990.
  12. The Wellcome Trust, “What is DNA?”: http://www.wellcome.ac.uk/en/imagine2003/DNA_what.html (accessed 8/10/03, no longer available online)
  13. Wikipedia, the free encyclopedia: http://en.wikipedia.org/wiki/Human_Genome_Project (accessed 8/10/03)
  14. WormBase — The Biology and Genome of C. elegans: http://www.wormbase.org/ (accessed 8/10/03)

Section: Ethical Implications

General References:

  • »Anderson, W.F. “Genetics and Human Malleability.” Hastings Center Report. Vol. 20, January-February 1990, pp. 21-24.
  • »Buchanan, A., Brock D.W., Daniels, N., and Wikler, D. From Chance to Choice: Genetics and Justice. Cambridge University Press, 2000.
  • »Holtug, N. “Altering Humans: The Case For and Against Human Gene Therapy.” Cambridge Quarterly of Healthcare Ethics. Vol. 6, no. 2, Spring 1997, pp. 157-174.
  • »Pelias, M.Z. and Blanton, S.H.. “Genetic Testing in Children and Adolescents: Parental Authority, the Rights of Children, and the Duties of Geneticists.” The University of Chicago Law School Roundtable. Vol. 3, no. 2 1996, pp. 525-43.
  • »Pelias, M.Z. and Markward, N. “Newborn Screening, Informed Consent, and the Future Use of Archived Tissue Samples.” Genetic Testing. Vol. 5, no. 3, 2001, pp. 179-85.
  • »Pelias, M.Z. and Markward, N. “The Human Genome Project and Public Perception: Truth and Consequences.” Emory Law Journal, vol. 49, no. 3, Summer 2000.
  • »Walters, L. and Palmer, J.G.. The Ethics of Human Gene Therapy. Oxford University Press, 1997.

author glossary

Bacteria artificial chromosome (BAC): is a relatively short, often circular, DNA sequence used for cloning in bacteria, usually E. coli. It is usually 150,000 base pairs long with a range from 100,000 to 300,000 base pairs.

Bioinformatics: The discipline that uses mathematical and informational techniques to solve biological problems, usually by creating or using computer programs, mathematical models or both. Applications of bioinformatics include data mining in and analysis of the data gathered in genome projects, sequence alignment, protein structure prediction, metabolic networks, morphometrics, and virtual evolution.

Dideoxy chain-terminating (or Sanger method): is a process used to sequence (read the bases) of DNA. It is named after Frederick Sanger who developed the process in 1965.

DNA (deoxyribonucleic acid): Polynucleotide formed from covalently linked deoxyribonucleotide units; serves as the carrier of genetic information.

Genes: the basic elements that act as templates to produce the proteins and structural components for a living organism. The regulated function of genes lead to healthy growth and development while non-functional or unregulated genes (mutations) may function to impede development, cause acute or chronic diseases, induce cancer growth, and reduce life expectancy. Genetics has become part of a multidisciplinary science. Gregor Mendel, who studied inheritance among plants, is the Father of Genetics.

Genetic engineering: Describe the process of manipulating genes in an animal or plant, outside of the organism’s normal reproductive process. It often involves the isolation, manipulation and reintroduction of DNA into model organisms, usually to express a protein.

Germline: Informal term for gametes, also called sex cells, that are the reproductive (germ) cells of animals.

Intron-exon boundary: Nucleotides within DNA that mark the begining and end of a sequence that does not encode part of a protein (intron) and the begining and end of a gene that encodes part of a protein (exon).

Nucleotide bases: a compound consisting of a nitrogenous base and a five-carbon sugar bound to one or more phosphate groups.

Open reading frames (ORF): A portion of the genome that potentially codes for a protein.

Phenylketonuria (PKU): A human genetic disorder that occurs in about 1 in 15,000 births, but the incidence varies widely in different human populations from 1 in 4,500 births among the Irish to fewer than one in 100,000 births among the population of Finland. PKU is caused by a defective gene producing a defective enzyme.

Polymerase chain reaction (PCR): is a molecular biological method for amplifying (creating multiple copies of) DNA without using a living organism.

Somatic cell: any of the cells of a plant or animal except the reproductive cells.

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