A Look Into the Human Genome Project

A Look Into the Human Genome Project

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A Look Into the Human Genome Project

Would people buy a set of books that repeated the same four letters in random order page after page? Or would this information be more convenient to the public if on a computer disc? Many people would agree with the idea that this set of books would be boring. Surprisingly, America and the rest of the world are buying the information in this set of books. In fact, these books contain the human genome. The mapping of the genome (or writing this set of books) is a 15-year project that has brought many ethical issues to attention.

History of the Human Genome Project
The United States Department of Energy and the National Institutes of Health joined forces in 1990 to kick off a 15-year effort to reach two goals:

Catalog the genes in human DNA
Determine the three billion bases (the four letters in the set of books) in human DNA that encode for genes (U.S. Dept. of Energy 1998).
On the international level, the Human Genome Organization (HUGO) was founded. Their goal is to encourage trading of research findings and techniques (National Reference Center 1998). From the national standpoint it brings back memories of The Manhattan Project. Internationally, this cooperation is unprecedented (Shinn 1996). Before the organization of the Human Genome Project, the Department of Energy had biologists and physicists studying the Hiroshima survivors. From this data a GenBank was made. This was the first database for DNA sequences (Gert, et al. 1996).
Watson, who won the Nobel prize for his discovery of the double helix, was appointed as the first director of the Human Genome Project. He appropriated three percent of his budget to ethical, legal, and social issues (ELSI) involved with the project (Shinn 1996). Even from the beginning it was anticipated that this project could have both positive and negative outcomes.

One goal to be reached after five years was to have markers every ten centimorgans (Gert, et al. 1996). This goal was stated in 1991 and achieved in 1994 - a year ahead of schedule - when a map with markers every two to five centimorgans was published (Casey, et al. 1995). Sequencing would then follow with a focus on areas of disease and in reducing human error. The main goal for the next five years would be markers every one centimorgan (Gert, et al. 1996).

Technical Aspects
Ideally, the final map will have both physical and genetic information.

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It will contain DNA markers at close intervals with precise locations (National Reference Center 1998). This feat will be difficult since individuals have a 0.1 percent difference in their DNA (Shinn 1996). There are also known differences in the genomes of females and males (Gert, et al. 1996). Aiding the human genome research is E. coli, fruit fly, mouse (U.S. Dept. of Energy 1998), archea bacteria and yeast genomes (Travis, "Biology" 1997). E. coli functioned as the original model for molecular research. The fruit fly has served as a historic model due to easy breeding and prior knowledge of the insect. The worm C. elegan is also useful because it has a comparatively small genome as compared to humans. All these genomes offer similarity to the human genome. Simplicity is also a key element with these genomes. Since these genomes are smaller than the human genome it is easier to develop techniques with them. They give a starting point in research because if two genes are linked in mice, it is probable that they are linked in humans (Gert, et al. 1996). Efficient techniques are needed since only 5 percent of the human genome encodes for genes. The other 95 percent of the genome is nongenic sequences often referred to as junk. This 95 percent is not part of the human genome goals to be meet in the next fifteen years (National Reference Center 1998).
There are many different techniques that have been tried in sequencing and mapping the genome. Some have diminished in use due to time and accuracy concerns. Once a map has been determined this information can be used to locate the gene(s) causing the disease and then fix it. This would enable us to not only cure a genetic disease we have, but stop it from appearing in future generations. This encompasses broader issues of genetic screening and gene therapy. A map could also lead us to finding evolutionary links between species by comparing other maps to ours.

One of the techniques used in mapping genomes is YAC - yeast artificial chromosomes technique. This is done by cloning large pieces of DNA in yeast. The overlapping segments are used to piece together the DNA (Gert, et al. 1996). YAC technology has lead to the mapping of chromosomes 3, 11, 12, 21, 22, and Y (Casey 1995).

RFLP technology, which locates variations, was one of the first used in mapping. In fact, it showed that mapping was possible. This technique was both expensive and slow. Replacing this technique is the polymerase chain reaction - PCR. PCR rapidly clones the existing DNA, so a larger amount of DNA is obtained. This now large amount of DNA can be sequenced with the aid of a primer (Gert, et al. 1996).

Positional cloning allows for characterization of a gene once its approximate location is known. This technique aided in identifying genes for breast cancer, diabetes, and Alzheimer's disease (Gert, et al. 1996).

Another method involves ESTs - expressed sequence tags - which are single stranded DNA. These DNA segments act as lures to identify a gene's sequence. However, this procedure cannot identify every gene and ignores many others (Travis, "Human Genome Project" 1998).

The shotgun method has been used for smaller genomes and may be applied to the human genome. This involves breaking the DNA into thousands of pieces. These fragments are sequenced and overlapping segments are matched to reveal the genome (Travis, "Human Genome Project" 1998).

Microsatellites are commonly used in mapping. Microsatellites are areas of repetitive DNA. The advantages of microsatellites include abundancy, variation and ability to be analyzed by PCR (Casey, et al. 1995).

Ethical Issues
For good or bad, many issues have surfaced which either enforce the project or destroy it. On the positive side is gene therapy, answers to evolution, possible explanations to the origin of man, and many others. Opposing this is human privacy, discrimination, and get rich schemes. An organization called ELISA was formed to deal with these issues and regulate the research. Other groups have joined the effort including the United Nations Educational Scientific and Cultural Organization (UNESCO).
UNESCO drafted a declaration on human rights regarding the Human Genome Project. They want an agreement on ideas such as:

The genome shall not give profit to anyone.
Risks and benefits should be weighed before any research is begun.
Discrimination based on genetics will not be tolerated.
Genetic data will be confidential.
Results and benefits of the research will have public access; it will not be sold to the highest bidder. (Wertz 1998).
A few states and the Equal Opportunity Commission have made laws that deal with the Human Genome Project. One example is that discrimination based on genetics is illegal (Casey, et al. 1995).
With thoughts of profit comes the issue of whether any part of the genome can be patented. Most scientists would agree that these patents are unethical, but others are blinded by the fact that money can be made. Watson, first director of the Human Genome Project, objected so loudly to the idea of patents that it eventually cost him his position (Gert, et al. 1996). Almost five years after Watson lost his battle a scientific race began. Venter and Perkin-Elmer intend to privately sequence the human genome in three years and at a small fraction of the cost. They stress that the urgency of having locations for genes that lead to disease is more important then accurately sequencing the whole genome. They believe the 99.99 percent accuracy set by the Human Genome Project scientists is unnecessary at this stage (Travis, "Human Genome Project" 1998). They will then patent this information and be able to profit.

A Personal View
After reviewing information on the Human Genome Project I believe that it is an ethical organization with realistic goals. It is showing foresight by forming groups such as ELSI to aid in solving any ethical issues that may arise. I feel there may be a larger moral issue involved if we did not try to sequence the human genome.
I know the genome mapping will greatly aid in medical research and alleviate much pain and suffering. Of course, "fixing" genes to prevent genetic diseases should be monitored or people may some day place an order for their children. Once gene therapy is developed further after the map is complete it needs to be limited. A genetic disease should only be cured for that generation, not all upcoming generations. Future generations can then decide if they want to live with this disease or go through the therapy themselves.

Another issue is that people will discriminate based on genetic composition of others. This can be dealt with by just testing for genes of concern, such as breast cancer genes that run in a family. All other genes will remain unknown and insurance companies or employers will have no basis for discrimination. This also borders on the issue of involuntary testing. The military branches are currently making it mandatory to give blood for DNA testing. I think everyone should have the right to decide if they want their DNA to be sequenced.

It appears that the race is now on to sequence the genome. The race between government and private industry can have many outcomes. If industry wins, patents will be applied for. I think this is an injustice. People should not be able to make money to tell me my genetic makeup. This information should be public access so further advancements can be made.

Looking to my future I may have to decide if I want to keep my genetic predisposition to sun cancer and colon cancer. I think personally I would not have these genes altered in any way. I believe that everyone has genetic uniqueness for a reason. If everyone cures every genetic flaw in their DNA, aren't we making clones of each other? Along with thinking of myself I will have to determine if the genetic background my future spouse has will be worth the risk of us bearing children with "bad" DNA. I think that naturally people look for companions they find attractive, therefore giving their children a higher likelihood of being attractive. However, I would hate to have to bring my genetic map along on a first or second date.

At this point the set of books with only four letters is being written and is ahead of schedule due to advancing equipment and techniques. Their goals are being met by using YAC technology, ESTs and microsatellites among others. If government wins the race everyone will have access to this invaluable information. If private industry wins these books may have a price tag too big for the common man. Ethical issues are being rised about what should be done with this information when it is discovered. Groups such as ELSI are working hard to keep this at a minimum. Overall, the human genome project can be a success. It will be a tool to possibly tell us our future and maybe more importantly our past.

Works Cited
Casey, Denise, et al. Five Years of Progress in the Human Genome Project. Obtained from the WWW 09/30/98: 12/95: http://www.ornl.gov/TechResources/Human_Genome/publicat/hgn/v7n3/04progre.html
Gert, B., et al. Morality and the New Genetics A Guide for Students and Health Care Providers. Massachusetts: Jones and Bartlett Publishers, 1996.

National Reference Center for Bioethics Literature. The Human Genome Project. Obtained from the WWW 10/08/98: 12/9: http://guweb.georgetown.edu/nrcbl/scopenotes/sn17.htm

Shinn, Roger. The New Genetics. 1st ed. Rhode Island: Moyer Bell, 1996.

Travis, John. Another human genome project: a private company's plan shocks the genetics community.

Travis, John. Biology's periodic table. Obtained from WWW 10/08/98: 03/01/97:

U.S. Dept. of Energy. Human Genome Project Information. Obtained from the WWW 09/30/98: 07/31/98: http://www.ornl.gov/TechRescources/Human_Genome/home.html

Wertz, Dorothy. The Gene Letter. Obtained from the WWW 09/30/98: http://www.geneletter.org/0398/UNESCO.htm
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