Applications and Issues of the Human Genome Project

David Boehm

Copyright 1999

The history of the human race has been filled with curiosity and discovery about our abilities and limitations. As an egotistical creature with a seemingly unstoppable desire for new accomplishments, we attempt feats with emotion and tenacity. People worldwide raced to be the first to discover the secrets and the ability of flight. Enormous amounts of monies were spent on sending people into space and the race to land on the moon. With the rapid growth of scientific knowledge and experimental methods, humans have begun to unravel and challenge another mystery, the discovery of the entire genetic make-up of the human body.

This endeavor, the Human Genome Project (HGP), has created hopes and expectations about better health care. It has also brought forth serious social issues. To understand the potential positive and negative issues, we must first understand the history and technical aspects of the HGP.

History of the Human Genome Project

The HGP has an ultimate goal of identifying and locating the positions of all genes in the human body. A researcher named Renato Dulbecco first suggested the idea of such a project while the U.S. Department of Energy (DOE) was also considering the same project because issues related to radiation and chemical exposure were being raised. Military and civilian populations were being exposed to radiation and possible carcinogenic chemicals through atomic testing, the use of Agent Orange in Vietnam, and possible nuclear power facility accidents. Genetic knowledge was needed to determine the resiliency of the human genome (1).

Worldwide discussion about a HGP began in 1985. In 1986, the DOE announced its' Human Genome Initiative which emphasized the development of resources and technologies for genome mapping, sequencing, computation, and infrastructure support that would lead to the entire human genome map (3). United States involvement began in October 1990 and was coordinated by the DOE and the National Institute of Health (NIH). With an estimated cost of 3 billion dollars, sources of funding also include the National Science Foundation (NSF) and the Howard Hughes Medical Institute (HHMI). Because of the involvement of the NIH, DOE, and NSF who receive U.S. Congressional funding, the HGP is partly funded through federal tax dollars (1). Expected to last 15 years, technological advancements have accelerated the expected date of completion to the year 2003. This completion date would coincide with the 50th anniversary of Watson and Crick's description of the structure of DNA molecule (3).

Human Genome Project Goals

The specific goals of the HGP are to::

  • Identify all the estimated 80,000 genes in the human DNA,
  • Determine the sequences of the 3 billion DNA chemical bases.
  • Store this information in databases,
  • Develop tools for data analysis, and
  • Address the possible ethical, legal, and social issues (ELSI) (3).

    Technical Aspects of the HGP

    The process of determining the human genome involves first mapping, or characterizing the chromosomes. This is called a physical map. The next step is sequencing, or determining the order of DNA bases on a chromosome. These are genetic maps (7).

    Mapping Strategies

    To sequence the human genome, maps are needed. Physical maps are a series of overlapping pieces of DNA isolated in bacteria (6). Physical maps are used to describe the DNA's chemical characteristics. Mapping involves dividing the chromosomes into fragments that can be propagated and characterized, and then ordering them to correspond to their respective chromosomal locations (7). Genetic markers are invaluable for genome mapping. Markers are any inherited physical or molecular characteristics that are different among individuals of a population. An example of a marker includes restriction fragment length polymorphisms (RFLP). RFLPs reflect sequence differences in DNA sites that can be cleaved by restriction enzymes. To be useful in mapping, markers must be polymorphic, or have more than one form among individuals so that they can be detectable in studies (7). Another marker is Variable Numbers of Tandem Repeats (VNTR), which are small sections of repeating DNA. VNTRs are prevalent in human DNA and can exist in wide variance of numbers. This variability gives individuals unique VNTR regions. This is the application behind solving crime cases with blood samples (1). A genetic map shows the relative locations of these specific markers on chromosomes (7).

    Used in RFLP markers are restriction enzymes. These enzymes recognize short sequences of DNA and cut them at specific sites. Since scientists have characterized hundreds of different restriction enzymes, DNA can be cut into many different fragments. These fragments are the DNA pieces used in physical maps (7).

    Different types of physical maps exist. Low-resolution physical maps include chromosomal (or Cytogenetic) maps that are based on distinctive banding patterns of stained chromosomes. High-resolution physical maps represent sets of DNA fragments that were cut by restriction enzymes and placed in order as previously described (7).

    Sequencing Strategies

    To sequence DNA, it must be first be amplified, or increased in quantity. Two types of DNA amplifications are cloning and Polymerase Chain Reactions (PCR). Cloning involves the propagation of DNA fragments in a foreign host. Known as recombinant DNA technology, DNA fragments isolated from restriction enzymes are united with a vector and then reproduced along with the vector's cell DNA. Vectors normally used are viruses, bacteria, and yeast cells. Cloning provides an unlimited amount of DNA for experimental study (7).

    With PCRs, DNA can be amplified hundreds of millions of times in a matter of hours, a task that would have taken days with recombinant DNA technology. PCR is valuable because the reaction is highly specific, easily automated, and capable of amplifying very small amounts of DNA. For these reasons, PCR has had major impacts on clinical medicine, genetic disease diagnosis, forensic science, and evolutionary biology (7).

    PCR is a process through which a specialized polymerase enzyme synthesizes a complementary strand of DNA to a separate given strand of DNA in a mixture of DNA bases and DNA fragments. The mixture is heated, separating the two strands in a double-stranded DNA molecule. The mixture is then cooled and through the action of the polymerase enzyme, the DNA fragments in the mixture find and bind to their complementary sequences on the now separated strands. The result is two double helix strands from one double helix strand. Repeated heating and cooling cycles in PCR machines amplify the target DNA exponentially. In less than 90 minutes, PCR cycles can amplify DNA by a millionfold (7).

    Now that the DNA has been amplified, sequencing can begin. Two basic approaches are Maxam-Gilbert sequencing and Sanger sequencing. Both methods are successful because gel electrophoresis can produce high-resolution separations of DNA molecules. Electrophoresis is the process of using gels with stained DNA and then separating those DNA fragments according to size by the use of electric current through the gel. Even fragments that have only one single different nucleotide can be separated. Almost all of the steps in both of these sequences are now automated (7).

    Maxam-Gilbert sequencing, also called chemical degradation method, cleaves DNA at specific bases using chemicals. The result is different length fragments. A refinement to this method known as multiplex sequencing enables scientists to analyze approximately 40 clones on a single DNA sequencing gel.

    Sanger sequencing, also called the chain termination or dideoxy method, uses enzymes to synthesize DNA of varying length in four different reactions, stopping the replication at positions occupied by one of the four bases, and then determining the resulting fragment lengths (7).

    A major goal of the HGP is to develop automated sequencing technology that can accurately sequence more than 100,000 bases per day. Specific focuses include developing sequencing and detection schemes that are faster, more sensitive, accurate, and economical (7). In 1991, computer technology entered the sequencing process at Oak Ridge National Laboratory where an artificial intelligence program called GRAIL was tested (1).

    Applications of the HGP

    Scientists estimate that chromosomes in the human population differ at about 0.1%. Understanding these differences could lead to discovery of heritable diseases, as well as diseases and other traits that are common to man (6). Information gained from the HGP has already fueled many positive discoveries in health care. Well-publicized successes include the cloning of genes responsible for Duchenne muscular dystrophy, retinoblastoma, cystic fibrosis, and neurofibromatosis (2). Increasingly detailed genomic maps have also aided researchers seeking genes associated with fragile X syndrome, types of inherited colon cancer, Alzheimer's disease, and familial breast cancer (3).

    If other disease-related genes are isolated, scientists can begin to understand the structure and pathology of other disorders such as heart disease, cancer, and diabetes. This knowledge would lead to better medical management of these diseases and pharmaceutical discovery (2).

    Current and potential applications of genome research will address national needs in molecular medicine, waste control and environmental cleanup, biotechnology, energy sources, and risk assessment (3).

    Molecular Medicine

    Through genetic research, medicine will look more into the fundamental causes of diseases rather than concentrating on treating symptoms. Genetic screening will enable rapid and specific diagnostic tests making it possible to treat countless maladies (3). DNA-based tests clarify diagnosis quickly and enable geneticists to detect carriers within families. Genomic information can indicate the future likelihood of some diseases. As an example, if the gene responsible for Huntington's disease is present, it may be certain that symptoms will eventually occur, although predicting the exact time may not be possible. Other diseases where susceptibility may be determined include heart disease, cancer, and diabetes (2).

    Medical researchers will be able to create therapeutic products based on new classes of drugs, immunotherapy techniques, and possible augmentation or replacement of defective genes through gene therapy (3).

    Waste Control and Environmental Cleanup

    In 1994, through advances gained by the HGP, the DOE formulated the Microbial Genome Initiative to sequence the genomes of bacteria useful in the areas of energy production, environmental remediation, toxic waste reduction, and industrial processing. Resulting from that project, six microbes that live under extreme temperature and pressure conditions have been sequenced. By learning the unique protein structure of these microbes, researchers may be able to use the organisms and their enzymes for such practical purposes as waste control and environmental cleanup (3).


    The potential for commercial development presents U.S. industry with a wealth of opportunities. Sales of biotechnology products are projected to exceed $20 billion by the year 2000. The HGP has stimulated significant investment by large corporations and promoted the development of new biotechnology companies hoping to capitalize on the implications of HGP research (3).

    Energy Sources

    Biotechnology, strengthened by the HGP, will be important in improving the use of fossil-based resources. Increased energy demands require strategies to circumvent the many problems with today's dominant energy technologies. Biotechnology will help address these needs by providing a cleaner means for the bioconversion of raw materials to refined products. Additionally, there is the possibility of developing entirely new biomass-based energy sources. Having the genomic sequence of the methane-producing microorganism Methanococcus jannaschii, for example, will allow researchers to explore the process of methanogenesis in more detail and could lead to cheaper production of fuel-grade methane (3).

    Risk Assessment

    Understanding the human genome will have an enormous impact on the ability to assess risks posed to individuals by environmental exposure to toxic agents. Scientists know that genetic differences cause some people to be more susceptible than others to such agents. More work must be done to determine the genetic basis of such variability, but this knowledge will directly address the DOE's long-term mission to understand the effects of low-level exposures to radiation and other energy-related agents, especially in terms of cancer risk (3). Additional positive spin-offs from this research include a better understanding of biology, increased taxonomic understanding, increased development of pest-resistant and productive crops and livestock, and other commercially useful microorganisms (8).

    Ethical, Legal and Social Implications

    Early planners of the HGP realized that human genomic mapping and sequencing would have profound implications for individuals, families and our society. Although this information can potentially and dramatically improve human health, it would raise a number of ethical, legal and social issues (ELSI) such as how this information would be interpreted and used, who would have access to it, and how can society prevent harm from improper use of genetic information. To address these issues, the ELSI Program was established as a part of the HGP. ELSI was created so that potential problem areas could be identified and solutions created before genetic information is integrated into modern health care practices (4). This is a unique aspect because the HGP is the first large scientific endeavor to address social issues that may arise from the project (3). The DOE and NIH genome programs each set aside 3-5% of their annual budgets for the study of ELSI (4).

    There are four major priorities being addressed by ELSI. The first is the issue of privacy and fairness in the use and interpretation of genetic information. As genetic information is being discovered, the risk of genetic discrimination increases as new disease genes are identified. The issue of privacy and confidentiality, including questions of ownership and control of genetic information becomes critical. Fair use of this information for insurance, employment, criminal justice, education, adoption, and the military is necessary. Also, the impact of genetic information on psychological responses to family relationships and individual stigmatizations becomes an issue (5).

    The second priority for ELSI is the clinical integration of new genetic technologies. It has been questioned if health professionals are adequately educated about genetics, genetic technologies and the implications of their use. Important issues include individual and family counseling and testing, informed consent for individual considering genetic testing, and the use of such genetic test for the use of reproductive risk assessment and making reproductive decisions (5).

    The issues that surround genetic research are the third priority of ELSI. Such issues include the commercialization of the products from human genetic research. Examples are questions of the ownership of tissue and tissue derived products, patents, copyrights, and accessibility of data and materials (5).

    The fourth priority is the education of the general public and health care providers. ELSI funded surveys have revealed that most of the public and health professionals are not knowledgeable about genetics, genetic technologies and the implications of having genetic information. It is essential that the public understands the meaning of genetic information and that the nation's health professionals have the knowledge, skills, and resources to integrate this new knowledge and technologies into diagnosis, prevention, and treatment of diseases (5).

    Personal Opinion About the HGP

    Although vast issues of social implications have arisen from genetic research, society has too much to gain from the discovery and consequent understanding of the human body and all its components. Americans alone spend enormous sums of money on personal health care including diet pills, hair loss, and virility drugs. It is unforeseable to me that our society will stop its' quest to be healthier and happier.

    I believe that genetic research and information should not be allowed in any discriminatory manner. Insurance companies should not be allowed to deny coverage to individual or even have access to that information. The rights of privacy need to be strengthened. Employers and employments agencies should not know an individuals' genetic information. This information should be for the individual at risk of health concerns only and used in treatment or possible prevention.

    To be valuable to society, genetic information must be available to all people in need of such information. Class distinctions between those who can afford better health care must not enter the use of genetic research and information.

    The positive endeavors such as environmental issues of clean-up and waste management, increased agricultural production and safe food quality should be strengthened.

    Genetic research is further extension for the human mind to understand our own beings. We desire information. I do not believe it is possible, if even necessary, to stop the advancement of scientific discovery. As a society and human race, the question that should be concerning and focused on is rather what issues resulting from this discovery need to be addressed. Our curiosity will not stop. Let us use new genetic information to advance the prosperity of the human population.


    1. The Human Genome Project. Obtained 10/13/99.
    2. What can we expect from the Human Genome Project. Obtained 10/13/99.
    3. What is the Human Genome Project? Obtained 10/2/99.
    4. Text from "New Goals for the U.S. Human Genome Project: 1998-2003," Science 282: 682-689 (1998). Obtained 10/2/99.
    5. National Human Genome Research Institute. Obtained 10/2/99. http://WWW.NHGRI.NIH.GOV/About_NHGRI/Der/Elsi/high_priority.html#Privacy
    6. The Human Genome Project. Obtained 10/16/99.
    7. Mapping and Sequencing the Human Genome. Obtained 10/16/99.
    8. Human Genome Project - Discovering the Human Blueprint. Obtained 10/16/99

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