The Human Genome Project

Chad Ringdahl

Introduction

The Human Genome Project is one of the most widely discussed topics in genetics today. The United States human genome project began in 1990, when the $3 billion dollar project to map 3 billion DNA base pairs was announced.(4) When the initial funding was provided, it was anticipated that the project would require 15 years to complete and the target date for completion was 2005.(8) Recent technological advances have shortened that time period, and it is now estimated that the program will be complete by 2003.(1) The program now has been expanded to an international effort involving research facilities in France, Germany, Japan, the United Kingdom and the United States. There are also several private companies that are sequencing the genome also. The majority of the funding for the United States human genome project has come from the Department of Energy's (DOE) Office of Biological and Environmental Research and the National Institute of Health (NIH). The objective of the project is to create a DNA sequence library for a representative sample of the human genome. Such a reference library would prove to be priceless from a research standpoint, as well as an applied perspective. This library will aid in the identification of specific mutations which cause a distinct disorder or disease. If the normal base pair can be inserted in place of the abnormal one, gene therapy could become a reality.

Along with this new technology comes several problems, both technical and ethical. The ethical issues play a major role in the use and possible implications of this technology. A special committee was formed to evaluate these ethical issues and to make recommendations regarding them. This committee was given the title "Ethical, Legal and Social Issues committee, ELSI.(7) This committee will be discussed in-depth later in this report.

Technical Aspects

The technical aspects of the genome project are relatively complex and still have issues to resolve. The Human Genome Projects goal is to produce a highly accurate reference sequence of the human genome. The human genome is composed of a single compound, DNA. DNA is basically just a sequence of different base pairs, adenine, cytosine, guanine and thymine, which are arranged in a double helix structure. Their purpose is to direct cell function and ultimately tissue differentiation. The DNA makes an organism what it is by directing the development of the body, including distinguishing characteristics and biochemical processes. The goal of the project is to sequence this sequence of DNA so that a map of it may be produced that shows the location and arrangement of all of the base pairs present in a human being. The level of accuracy of the DNA sample is 1 error in 10,000 base pairs.(1) The sample should be largely continuous across each human chromosome. The vast majority of human DNA is similar from individual to individual with differences occurring only at specific areas. The project plans to map 80,000 human genes to specific chromosomal location prior to it's completion. When the American genome project was formed the question of how to obtain a representative sample was raised. The decision was made that a DNA sample would be obtained from four individuals. This was further complicated when it was found that the DNA came from a limited group of donors in regards to the entire human population. Three men and one woman were selected. Worse yet, it is believed that consent to make the DNA sequence public information was not obtained from the donors.(3)

The sequencing of the human genome has proven to be a tedious and difficult undertaking. An enzyme, gyrase, is used to unwrap the DNA double helix. Then helicase cleaves the double stranded structure into two chains of DNA. Then another enzyme is added to break the DNA chain at certain known points. DNA clones are used to capture the sequence of the DNA that is present. These BAC's typically contain 100-200 kb inserts of human DNA that is stable and could represent the human genome well.(4) Once these human DNA clones are produced, a computer sorts out the sequences according to known sequences. The computer than reads what DNA bases are present and stores this genetic information for latter construction of chromosome maps and construction of a working model of the genome. This sequencing takes place continuously and is automated. There are often many sequences running at the same time in the same lab.

Potential Uses of the Human Genome Project

The potential uses of the data obtained from the Human Genome project are virtually infinite. The project was initiated as just a pure research program to study how DNA functions and how human phenotype varied according to genotype. In the past few years, the project has been viewed in a more applied manner. Many feel that the genetic sequences recorded by the project will aid in the identification of genetic links to human disease. Once the causes of these diseases are discovered and understood, there is hope that defective genes may be repaired and the disease cured.(5) Already, the genes responsible for cystic fibrosis, breast cancer, colon cancer and sickle cell anemia have been found, making genetic tests for carriers of the disease a reality.(2) This testing also raises some serious ethical and social issues.

Ethical Issues

The ethical and social issues associated with the Genome Project have spurred a great deal of concern from the general public and researchers working within the project itself. These concerns lead to the formation of the ELSI committee of the human genome project. In 1997, the ELSI project received 11 million dollars of the Human genome budget, to study the implications of the Human Genome Project.(5) The ELSI committee has looked at many interrelated issues associated with the genome project. One such issue that has been investigated is the potential for gene therapy. Gene therapy involves locating a defective allele in an individual and replacing it with the correct allele. The genomic library created by the genome project will provide a way to determine what the correct sequence is at a particular loci and the correct base pairs may be able to be inserted into the affected individual if technology advances to that point. This has caused concern with many people because they feel that in a way mankind will be altering nature by eliminating the defective alleles from a population. Some say that by doing that we are in a sense creating super humans that have few if any genetic defects. This raises ethical concerns because some religious groups feel that mankind would be taking the role of the supreme creator if gene therapy becomes a reality. Currently molecular genetics has been able to identify metabolism defects due to a genetic alterations, the metabolite is then synthesized in a lab and injected into the affected individual thus relieving them of the disease condition. This too may have ethical implications because we are correcting a deficiency that was present at birth, thus altering the course of nature.

Discrimination based on genotype has also been raised. For example, employers may obtain genetic information on employees prior to hiring them. If a certain employee is shown to be genetically susceptible to undesirable work force traits they may be discriminated against. The same case is also possible with insurance companies. Health insurance companies may gain access to genetic information on an individual and thus discriminate against them, by refusing coverage or charging higher insurance premiums. If an individual is a carrier of alleles which have been associated with a particular disease it may make obtaining health insurance nearly impossible for the afflicted individual. If a genetic linkage is discovered that links alcohol abuse with a certain allele, auto insurance companies may also discriminate against such individuals by charging a higher premium. Congress has already enacted legislation banning discrimination based on genetic knowledge, so this may not be a major issue regarding the Human Genome Project.(6)

The Genome project may answer questions regarding evolution. By comparing human DNA with primate DNA, it may be possible to piece together the evolution puzzle. The possibility of unraveling the evolution puzzle has caused great controversy from religious groups around the world. If it is proven scientifically that evolution did in fact occur in humans, it would shake the ground work from which many religions are based on. This would have serious implications on the beliefs that have held true for centuries. Many feel that this is an area that should be left alone and not explored, due to the sensitivity of the potential findings. Although, if it were to be found that evolution did take place from the primates, it could possibly expand the potential uses of primates as genetic test subjects. If there was similar DNA at a specific loci, genetic tests could be performed to determine gene action and this could be applicable to human molecular genetics.

The genome project will also lead to improved techniques of genetic screening for diseases prior to birth. The genomic library created by the Genome Project will contain genetic information of fairly homogenous regions of the human genome, therefore there won't be a great deal of variability between individuals at these loci. If a genetic disease is found to be produced from a specific mutation or allele being present, screening can occur to determine who these individuals are. By analyzing the gamete DNA from parents, it is possible to determine the probability a child might inherit genetic disorders from the parents. This can be adventitious from the standpoint of potential gene therapies. It could allow genetic disorders to be corrected before birth. This has sparked the debate over whether or not it is ethical to pre-select the genotype of the child they have. If genetics advances to the point of rapid selection and insertion of DNA into human individuals, "designer" children could potential become a reality. Parents may want to select children that were genetically predisposed for intelligence, athleticism or some other desirable trait.

Genetic tests may also be beneficial to people that have mutations at certain loci that make them particularly susceptible to an environmentally induced disease. Thus, they could potentially avoid the disease by avoiding the environment that could cause the disorder.

Another concern with the Human Genome Project relates to the monetary returns generated by it. It has been asked many times, "Who will receive the monetary benefits of this research if anyone?" This has been a major debate ever since the conception of the Human Genome Project, because the majority of the research is being funded by federal funds. The American society seems to feel that since they have funded the research through their tax dollars, they should receive this information free of charge. There have been numerous private companies that have begun sequencing the genome in hopes that they will be able to receive a great deal of financial gain from it. Thus the question remains, "Who owns the information generated by the project?" Already a trend has begun where a private company will patent a gene that it sequences. Many feel that such important information regarding the essence of life should be available to all mankind without a cost, but unfortunately the research required to obtain that information is very costly. Regardless of the issue involved, it has become apparent that intense regulation will have to be put in place, to insure that the information gained from the Human Genome Project is used correctly and for the benefit of all mankind. Such regulatory agencies should be comprised of individuals representing different facets of the debate. This way all viewpoints can be expressed, and all concerns can be heard.

Conclusions

The one thing that everyone seems to agree on is that the Human Genome Project will have profound effects on human life regardless of it's use. It appears that everyone will be touched by it in some way. I personally feel that it is an excellent project, with very good intentions. The ultimate goal of the project is to understand the true essence of what makes mankind what we are. Never before has such a project been initiated whose goal is to understand the actually backbone of human life. With this knowledge comes very important responsibilities with which all of mankind should be concerned with. The regulation of the information gained from the project appears to be a greater challenge then unraveling the mysteries of life itself. I feel that the beneficial applications of this project outweigh the potential negative effects. Any application of the Human Genome Project should be evaluated carefully before it is applied to human subjects. If this is done many of potential problems can be avoided before they occur. Never before has man had the ability to obtain this genetic knowledge and with any new technology there will be problems along the way. My main concern is that science will use the information gained from the project to go beyond our human bounds and ultimately play a creator of sorts. If mankind attempts to manipulate the natural processes of reproduction and gene flow it ultimately could lead to the downfall of the human species by creating a limited gene pool. I feel genetic diversity is what allows a species to survive despite changes in environment.

I believe that one of the most important issues regarding the information gained from this project is the issue of discrimination based on genetic information. I feel that ones genetic information is something that requires the utmost privacy, for these genes are what make us who we are. If companies or employers were to obtain this information it could lead to discrimination with no basis. Just because someone carries genes that make them susceptible for a certain condition doesn't necessarily mean that the condition will be present. Many of the diseases and conditions that occur are due to an interaction of environmental and genetic factors. Therefore, if someone did have a undesirable gene in their genome, they may not ever develop the condition if the environmental conditions are not present for it's development.

I believe that the Human genome project may shake the very ground work that our society is based on, in regards to religion and age old beliefs about fate, and inheritance. Nonetheless this knowledge must be gained because it is in the natural order of advancement of knowledge. We are required to gain this knowledge because for the first time in history we have the tools to do it. With proper management and caution I feel that the Human Genome Project can benefit all of mankind with the some of the greatest discoveries of all time.

References

1. Marshall, Elliot. "New Goals for the U.S. Human Genome Project: 1998-2003". Science. Vol. 282, p. 682-688. October 23, 1998.
2. Marshall, Elliot. "The Genome Program's Conscience". Science. Vol. 274, p. 488-490. October 25, 1996.
3. Marshall, Elliot. "Whose Genome Is It, Anyway?". Science. Vol. 273, p. 1788-1789. September 27, 1996.
4. U.S. Dept. of Energy. Human Genome News. "BAC End Sequencing Speeds Large and Small Projects", Obtained from the WWW 9/2/99:2/1/99: http://www.ornl.gov/hgmis/publicat/hgn/v10n1/04bacend.html
5. U.S. Dept. of Energy. Human Genome News. "Five years of Progress in the Human Genome Project", Obtained from the WWW 09/07/99: 12/95: http://www.ornl.gov/TechResources/Human_Genome/publicat/hgn/v7n3/04progre.html
6. UNESCO. The Gene Letter. "UNESCO Declaration on the Human Genome and Human Rights, July 1997", Obtained from the WWW 09/07/99:07/99: http://www.geneletter.org/0398/UNESCO.htm
7. U.S. Dept. of Energy. Human Genome Project: "Ethical, Legal and Social Issues (ELSI) of the Human Genome Project", Obtained from the WWW 08/31/99: 08/31/99: http://www.ornl.gov/TechResources/HumanGenome/resource/elsi.html
8. U.S. Dept. of Energy. Human Genome News. "U.S. HGP on Fast Track for Early Completion", Obtained from the WWW 8/31/99:2/1/99: http://www.ornl.gov/hgmis/publicat/hgn/v10n1/01goals.html

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