THE HUMAN GENOME PROJECT
Jim Dodds and Sandra Enger
Suitable for grades 9-12.
To stimulate growth in students' abilities to analyze some of the novel ethical issues which are expected to arise as a result of knowledge developed in the coming decades by the Human Genome Project.
The basic strategy of the module is to pose an ethical dilemma, then counter the
student's response with a countervailing consideration. One alternative is to do
this as a whole-class activity, with attention directed to a projection screen.
When "Genome Project" is opened, the following text appears on the screen:
Pick your topic:
Pick your topic:
The teacher clicks on a button at the bottom of the screen to select the topic. A fact situation is then presented on the screen, with a choice to be made. The teacher invites the class to discuss the fact situation and make a consensus choice. Clicking on the button for that choice then brings up a screen which gives a contrary view. This can then be the basis for further discussion and possible refinement of the class' view of the ethical question presented.
If a palette is not available, all the screens can be printed using the " print stack" command under the file menu. This "hard copy" can then be used as transparency masters. The disadvantage of this approach is that, throughout the lesson, the teacher must find the appropriate transparency for each choice made.
A third option is to let students work in pairs or groups of 3 or 4 at computers. To employ this option, the teacher needs only to copy Hypercard 2.1 and Genome Project onto the hard drive of each computer in the lab.
The text on any of the screens can easily be edited by the teacher, just as with a word processor. More elaborate changes (adding cards or buttons) can also be made by a teacher with an elementary knowledge of Hypercard programming. We invite your suggestions for improving and updating the software.
The Human Genome Project
The Human Genome Project (HGP) is a project which has as its ultimate goal the identification and location of the positions of all genes of the human species. The actual sequence of the nucleotides making up the genes will also be another part of the project. Nobel laureate Walter Gilbert described the human genome as the Holy Grail of biology.
The concept of developing this project began to take shape during the late 1960's and throughout the 1970's. When the first maps of genes were conceived, these maps were based on direct observation of chromosomes. Patterns of familial inheritance of genetic based disorders such as Huntington's disease were studied to deduce the possible mode of inheritance.
As biochemical analysis of DNA became possible, segments of DNA associated with a pattern of inheritance were identified. These segments of DNA, called markers, allowed scientists to begin to identify regions of chromosomes that coded for genetic disorders. As biotechnological techniques developed, DNA sequencing became possible, and the nucleotides in a chromosomal region or a gene could be determined.
Renato Dulbecco was the first researcher to suggest publicly the idea of a human genome project. The U.S. Department of Energy (DOE) was also considering such a project because legal issues related to radiation or chemical exposure were surfacing. Military personnel and civilian populations had been subjected to radiation exposure during atomic testing. Vietnam veterans had been exposed to Agent Orange. Nuclear power facilities posed possible radiation exposure to employees and to the general public in the event of an accident. The resiliency of the human genome was of interest, and a genetic knowledge base was needed to assess this resiliency.
The debate to organize the HGP dates back to 1985. Italy began a genome project in 1987. The United Kingdom and the former U.S.S.R. began projects in 1988. Japan has also begun a project, and the U.S. project officially began in October 1990. The U.S. project was projected to cost 3 billion dollars over 15 years. The major sources of funding in the U.S. are the National Institutes of Health (NIH), the United States Department of Energy (DOE), the National Science Foundation (NSF), and the Howard Hughes Medical Institute (HHMI). NIH, DOE, and NSF receive funds appropriated by Congress which means the project is being supported in part by federal tax dollars. Funding from the private sector also contributes to the HGP.
The HGP is not only collecting information about the human genome; some researchers are also working on the genomes of other organisms. Some of the organisms being used in the HGP include Escherichia coli, a bacterium, Saccharomyces cerevisiae, a yeast, Drosophila melanogaster, the fruit fly, Caenorhabditis elegans, a nematode, and Mus musculus, the mouse. More sophisticated techniques related to gene identification and DNA sequencing are being developed by many research laboratories as the project progresses.
The question might be posed: what is the value of working with organisms other than humans? The genetic information of the other organisms can be manipulated in various ways in the research laboratory to elucidate information related to the genome. Understanding variation, developmental biology and gene regulation are also anticipated outcomes of this aspect of the HGP.
The enormity of the HGP may be placed in some perspective if the task of sequencing the base pairs in some selected organisms is considered. The number of base pairs in the haploid DNA of E. coli is 4.7 million pairs, and S. cerevisiae has 15 million pairs. D. melanogaster has 155 million while C. elegans has 80 million. M. musculus has 3,000 million. Haploid human DNA is projected to have 2,800 million base pairs which represent at least 50,000 to 100,000 genes.
With the monumental task of trying to decode the human genome comes the necessity to improve and refine techniques for identifying genes and base sequences. In sequencing DNA, DNA must first be cloned or isolated in some way. DNA requires laboratory preparation for sequencing analysis, and the sequencing reactions which are done involve either chemical or enzymatic protocols. Sequencing gels are run and further processed before DNA sequences can be deciphered. To speed the sequencing process, automated and computerized technologies are being developed. Even with automated sequencers the process is slow. In 1991, 2,000 bases could be sequenced per day. At this rate, it would take 1.5 million person days to sequence the entire genome.
With all of the information generated from this project, new databases are being established. Some of these databases have information about specific research techniques while others include lists of researchers. Computer technology has also entered the DNA sequencing process. In 1991, Oak Ridge National Laboratory was testing an artificial intelligence program which was called GRAIL. A "DNA chip" is also a computerized sequencing application.
The DNA library will continue to expand, and with this increased information, new problems of a different type are surfacing. As the information regarding the human genome expands, we will be able to access information about our own genetic makeup. Genetic based diseases can be detected or predicted. The genetic constituency of an embryo could be surveyed for potential problems. Genetic disorders for which there are no existing corrections will be detected. Also, questions as to who should have access to your genetic profile will surface. What will employers and insurance companies do with such information? What kinds of psychological implications does this present an individual who will develop an untreatable disorder at age 40?
Whose genome will be selected as the information base for the HGP? Actually, the DNA library that is developed will represent a profile compiled from many individuals. The information will be similar to having a catalog of many different genetic variations.
Some Techniques Used in the Genome Project
Restriction Fragment Length Polymorphisms (RFLPs)
Each restriction enzyme is specific to a certain base sequence (" restriction site") and will cut DNA at all such sites to produce a number of "restriction fragments". No two individuals will have exactly the same base sequence unless they are identical twins. Because of this DNA variability, restriction fragments from a given region of an individual's genome can be separated using gel electrophoresis to reveal a unique pattern ("fingerprint"). Inheritance of RFLPs can be followed through families. By using RFLPs scientists are able to construct linkage maps.
A type of RFLP called a variable number of tandem repeats (VNTR) has application in forensics. DNA has repeated numbers of regions which are noncoding regions. A VNTR is a small section of repeating, noncoding DNA. VNTRs are scattered throughout a person's DNA, and the number of repeats can vary from a few to a few hundred. This variability gives an individual unique VNTR regions. Even the homologous chromosomes of a person tend to differ. Because of these differences, the VNTRs in an individual's DNA can be used to identify with near certainty the confirmation or rejection of an accused person in crimes such as murder or rape where a small sample of blood or semen is collected.
Automated DNA Sequencing
Lloyd Smith and Leroy Hood of Caltech developed an automated sequencing process that is used to speed up the task of DNA sequencing. The technique makes use of at least four different fluorescent dyes that attach specifically to either adenine, thymine, guanine or cytosine. Restriction fragments are tagged with dye. The dyed fragments are passed through a glass tube that is filled with a special transport gel. Small DNA fragments move through the gel more rapidly than larger fragments.
When the fragments reach the end of the gel, they are excited by a beam from an argon-ion laser. Each dye will fluoresce with a different color. Light emitted by the fluorescing dye is sent to a photomultiplier and then converted to a digital signal. A computer program is able to differentiate among the signals and, in turn, order the sequences of bases on the DNA fragments.
Polymerase Chain Reaction (PCR)
Using the polymerase chain reaction (PCR), millions of copies of a specific DNA segment can be made in a test tube. PCR is also an automated process. Many physical mapping strategies depend on creating an array of linear DNA overlaps. Multiple copies of DNA fragments are needed to complete the mapping process. PCR can be applied for forensic purposes as well. From a very tiny amount of DNA, the polymerase chain reaction can be used to produce more copies of the DNA for analysis.
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