dna.gifThe Human Genome Project:
A Focus on Genetics and the Social and Ethical Implications


Introduction


The human race has always been concerned with looks. Many people want a certain hair color, skin color, or eye color, which has caused an infatuation with hair dye, self-tanner, and colored contacts. This obsession with appearances has surrounded me for as long as I can remember. I couldn’t walk past the newspaper stand on my street corner without noticing a magazine cover raving about the skinniest, best-tanned, "beautiful" girl. When I learned about the Human Genome Project, I couldn’t imagine how much more appearances would be able to dominate our culture.

The Human Genome Project (HGP), completed in 2003, was created to sequence a human’s DNA, store it, and develop tools to analyze it.[1] In studying that DNA, the HGP team uncovered the genes that produce pigmentation and those that control gender. Humans would be given the opportunity to morph the genes of their children during embryonic development.[2] For a hefty price, parents would even be able to control the sex of their children, along with hair color, skin color, and eye color.

The HGP also intended to address the moral and ethical complications associated with gene therapy. According to the Bible, everyone is supposed to be acceptable in God’s eyes, which then causes questions to arise about the faith of a person who wants to use gene therapy. There are several other ethical questions: who should have access to a person’s genetic information? How will altering appearances affect minorities? Do we distinguish medical treatments from physical enhancements? Should parents have the right to alter their children’s genes? Who can determine if any of the data analyses, concluded results, and treatments are even accurate?

The most life-enhancing goal of the HGP, to uncover information that could aid human life and health, also caused its biggest ethical question: will society be able to handle life-changing information about ourselves, humans?

(DNA photo source: [3] )


Background and History


In October 1990, the U.S. Department of Energy and the National Institute of Health began the $13-billion project, which was expected to take 15 years.[4] James D. Watson
james_d-1._watson_300.jpg
James D. Watson
of the National Institute of Health was the main leader of the project, and the sequencings were done at universities and research centers across the globe.[5] The “HGP team” consisted of hundreds of scientists, professors, geneticists, and researchers from all over the world. Several countries participated in the project along with the United States, including the United Kingdom, France, Germany, Japan, China, India, Canada, Australia, Brazil, Denmark, the European Union, Israel, Italy, Korea, Mexico, the Netherlands, Russia, Sweden, and New Zealand.[6] The goal of the HGP was to label the estimated 20,000-25,000 genes encoded in our DNA.[7] Labeling these genes would allow scientists to study genetic disorders. One of the hopes for the project was to uncover enough information that scientists could pinpoint mutations and possibly correct them, freeing the individual of the disorder. The creation of the HGP was provoked by questions concerning the sequence of DNA and the possible health benefits of knowing our genetic code.

Long before the idea or creation of the HGP, Watson and Crick published the structure of DNA, allowing the public to have insight into
watson-crick_discover_dna.jpg
James Watson and Francis Crick
the potential of DNA. Their publication in 1953 provoked many questions about how DNA worked and how DNA studies would benefit humans. Scientists had not yet identified very many details about the actual information encoded in our DNA, though. They had realized the potential of the code, but they needed to know the precise sequences in order to understand how specific genes and traits were expressed. Scientists and medical professionals alike expected that DNA sequencing would provide in-depth knowledge of genetic diseases, eventually allowing scientists to uncover how to correct those disorders. Many concluded that DNA sequencing had the capability to help doctors provide proper medical treatment, which would help patients to live longer lives.

The United States President Bill Clinton and the British Prime Minister Tony Blair announced the completion of a rough draft of the genome in 2000.[8] It was essentially completed in April 2003, which was two years earlier than expected.

The HGP does not have a long or deep history, as the concept of DNA sequencing is very new in the overall timeline of genetics advancements.

(James D. Watson photo source: [9] )
(James Watson and Francis Crick photo source: [10] )



Explanation and Connections


What is a genome anyway? Why should you care? A genome is the genetic make-up of an organism—all of its DNA. DNA gives the cell instructions to encode specific amino acids, which are the building blocks for proteins. Proteins determine how your body will look, act, and live. Without DNA, your body wouldn’t know how to function—your body wouldn’t even be a body!

This seemingly complex code is only made up of four letters. That’s right, four letters. You’re existence on this planet is controlled by four letters! A (adenine), C (cytosine), G (guanine), and T (thymine) are the four bases that make-up DNA. DNA is one very long strand of As, Cs, Gs, and Ts. The order of these letters is unique to each person; no two people have the same DNA. For this reason, we have diversity in the world. Diversity, however, is not the point of the HGP. Scientists desired to examine the parts of the human genome that are very similar from one human to another. The HGP team wanted to find the genes that are universal between humans so that those genes could be examined and tested for possible treatments. Those treatments of and attentions to primarily universal genes would then benefit the greatest possible number of people.

Almost needless to say, the human genome is very large. We humans have about 3 billion base pairs![11] I liked the analogy I found at one website: "If the DNA sequence of the human genome were compiled in books, the equivalent of 200 volumes the size of a Manhattan telephone book (at 1000 pages each) would be needed to hold it all." [12] I enjoyed this one as well: "It would take about 9.5 years to read out loud (without stopping) the 3 billion bases in a person's genome sequence. This is calculated on a reading rate of 10 bases per second, equaling 600 bases/minute, 36,000 bases/hour, 864,000 bases/day, 315,360,000 bases/year."[13] I hope you can now at least somewhat imagine the enormity of the human genome. To store all of this information, scientists have calculated the base pair per megabyte ratio (1 million base pairs to 1 megabyte).[14] Three gigabytes are needed to store the 3 billion base pairs, and that’s without any annotations, calculations, examinations.[15] As our examination and knowledge of the human genome grows, though, we are bound to make more discoveries that require more and more computer space!

The HGP was completed in simultaneous steps, allowing many aspects of the project to be completed efficiently. These are the prominent steps and accomplishments:[16]

Screen_shot_2010-05-30_at_10.26.52_PM.png


As you can see, human DNA was not the only DNA sequenced. Model organisms were used as well to be a low-cost method to study gene inheritance. Mice, a type of model organism, have brief generations, but more importantly they have genes very similar to those of human’s. The comparison of model organism DNA with human DNA allows scientists to see the similarities between living things, which uncovers the genes necessary for life. My research will focus on processing human DNA specifically, though.

Scientists gathered DNA from the blood of women and the sperm of men, making random selections from a pool of donors; neither the donors nor the scientists know whose DNA was sequenced. [17] If the identity of the donor had been exposed, the donor’s personal and medical privacy would be extremely vulnerable to all kinds of controversies and problems, which I will discuss later.

In order to break apart the chromosomes, the HGP team used a process similar (but more complex) to this one (for more in-depth details on the process, please visit this website) :[18]


  1. Subcloning step: Chromosomes range in size from 50 million to 250 million bases, so they must be broken into shorter pieces for examination.
  2. Template preparation and sequencing reaction step: These short pieces are used as templates to make a set of fragments that differ in length from each other by a single base. That single base is like a tag that will identify the order of the strands in a later step.
  3. Separation step: These fragments in a set are sent through and separated by gel electrophoresis. (Gel electrophoresis is a method of separating and analyzing DNA strands using positive and negative charges.) Fluorescent dyes are used to tag the fragments, allowing there to be clear separation in a single lane on the gel.
  4. Base-calling step: The tagged base from Step 2 is identified. This identification allows the short strands to be reordered in their original sequence of As, Ts, Cs, and Gs. Currently, gel electrophoresis can only process 500 to 700 bases per reading.
  5. Analyzing step: Automated sequencers analyze the electrophoresis results, called electropherograms. The sequencers produce a chromatogram, or a graph that uses peaks to show the different components of a mixture, in order to examine where the different DNA bases are located. Computers are then able to assemble the short fragments into the correct order, processing about 500 bases at a time. After the fragments have been assembled, the computers act like spell-checkers, looking for errors. Once all errors have been removed, the computers examine gene-coding regions and other characteristics—they finally look at the genes! The finished sequence is stored in a database that anyone around the world can see, as it is online, free, and public.


Even though computers can do a lot of this work, and they did, there are over 3 billion base pairs in the human genome that needed to be sequenced—500 at a time is a snail’s pace! The HGP headquarters sectioned off the DNA and sent a different segment to each university and research center that was participating in the HGP.[19] Even though there were multiple machines and professionals working on the genome, only so many computers and gel electrophoreses can process at once and accurately; the project still took 13 years to complete.

I have included a YouTube video on gel electrophoresis to further illustrate the process:







Here are some connections to our class:

1) DNA Structure and Replication: In our genetics class, we leaned about the structure of DNA and how it replicates. This was extremely helpful knowledge to have when researching the HGP, as the purpose of the HGP is to examine DNA. The structure of DNA is in a double helix with the complimentary bases on the inside and a sugar-phosphate backbone on the outer structure. During the template preparation and sequencing reaction step of DNA sequencing, the HGP team uses a replication concept that I am familiar with: templates. They apply the idea that the complimentary bases only pair with one of the other bases (A with T, and C with G). Through using templates and DNA replication, they were able to create the fragmented template strands of DNA, which I described in the DNA sequencing process above.

2) DNA Transcription and Translation: Our genetics course has taught me about how DNA uses its information to create proteins. In understanding the purpose behind the HGP—to discover the thousands of genes in the human body—I needed to know how the genes actually translated into traits that were physically expressed. DNA transcription entails the “transcribing” of the DNA sequence to a strand of messenger RNA (mRNA). This mRNA then leaves the nucleus to be “translated” (DNA tranlation) into a chain of amino acids by ribosomes and transfer RNA (tRNA). The amino acid chains then compose proteins. As stated in sections above, proteins control how you look, act, function, and live. Without a thorough understanding of DNA transcription and translation, I would not have understood how the sequences uncovered in the HGP affected tangible human attributes.



Social and Ethical Implications



I have created a mind map to illustrate the many social, ethical, and moral questions and implications associated with the HGP:



[20]

Among them all, I have especially drawn an interest to the medical treatment versus physical enhancement dilemma. Scientists cannot be sure how DNA sequencing information will be used in the future. Once our society moves past beneficial medical treatments, society will have to debate whether it is socially acceptable to modify the physical appearance of a child during embryonic development.

It is only fair to consider both sides of the argument: For the pros, parents think they are helping their child, as a "beautiful" child may have an easier time making friends or finding love relationships. These desirable traits could help their child be "popular" in school, ultimately giving the kid overall happiness and satisfaction. For the cons, the child will not have a choice in the matter, and the child will never know if it would have preferred its original appearance. Also, the parents don’t know how the child will actually look until he or she is born, and they may be upset with their choices of colors or attributes. The parents would face the dilemma of whether or not to tell the child of their enhancements. If the child found out, he or she will most likely suffer from psychological problems throughout his or her life, such as identity confusion, low self-esteem, and difficulties in social environments. The child may feel like their parents wouldn’t have loved them had he or she not looked a certain way. These cons further emphasize appearances in society, rather than internal qualities and individuality. In my opinion, these pressures are exactly what our society doesn’t need. Magazines already flaunt the "best attributes," even though there has yet to be an omnipotent or omniscient individual to legitimately define these supposed superb qualities. Even if parents are simply choosing the sex of the child, there can be psychological problems. Once the child discovers that he or she was a transgender embryo, he or she is bound to have identity confusion, questioning whether or not he or she is a girl or boy.

Some people may suggest withholding the knowledge of the enhancements from the child, but then the question becomes about the ownership and privacy of medical records. A person’s medical records are their own, not their parents’. Even if parents try to hide the procedures, that child’s medical records will become the child’s property upon his or her 18th birthday. (That would be one surprising birthday present!) That child would then suffer from serious psychological problems, especially since the parents concealed the information.

This is a YouTube video of a CNN news segment on the possibility of “Designer Babies,” babies that parents can genetically "design" during embryonic development:






Society and the HGP team have yet to settle these social, ethical, and moral problems or define answers to the many unresolved questions. For many of the problems, scientists and medical professionals could put parameters around the uses of sequencing, such as creating a law that only enables disorders—not any physical enhancements or embryonic alterations—to be corrected. Again, however, there arises the problem of medical information as property: if the code is the property of the individual, then shouldn’t that individual be able to do whatever he or she wants with it, including physical enhancements? As you can see, there are endless questions about the effects of DNA sequencing.


Potential Futures


The Human Genome Project has many possible effects on the future, many of which will be determined after the ethical, moral, and social problems are addressed. Nevertheless, experts and observers predict that the HGP will cause biology and genetics to be the leading sciences of the 21st century.[21] Many people have already jumped on the genetics bandwagon, which is proven by the most recent Nobel prize going to telomere research. Experts suggest that DNA sequencing has truly remarkable potential benefits, including molecular medicine, energy sources and environmental application, evolution and human migration, DNA forensics and identification, and agriculture.[22] DNA sequencing may be the solution to many of the problems that society faces today, such as the Green House effect, as understanding and examining our chemical make-up can help us become more efficient in the world around us. Advancements in molecular medicine would also be hugely beneficial in helping the fight against cancer and AIDS, two leading causes of death; imagine a world where everyone was perfectly healthy—with healthful DNA—and no one died at an early age! But these benefits can only develop after debates are settled about the privacy and property rights of DNA sequences. DNA sequencing has a very positive future overall, though, and the future discoveries and advancements will prove the importance and success of the HGP.



  1. ^ http://www.ornl.gov/sci/techresources/Human_Genome/project/about.shtml
  2. ^ http://en.wikipedia.org/wiki/Human_Genome_Project
  3. ^ http://www.linnaeus.uu.se/online/phy/microcosmos/gifs/dna.gif
  4. ^ http://www.ornl.gov/sci/techresources/Human_Genome/project/about.shtml
  5. ^ http://www.ornl.gov/sci/techresources/Human_Genome/project/about.shtml
  6. ^ http://www.ornl.gov/sci/techresources/Human_Genome/faq/faqs1.shtml
  7. ^ http://www.ornl.gov/sci/techresources/Human_Genome/project/about.shtml
  8. ^ http://en.wikipedia.org/wiki/Human_Genome_Project
  9. ^ http://elementy.ru/images/news/james_d._watson_300.jpg
  10. ^ http://mikeely.files.wordpress.com/2009/02/watson-crick_discover_dna.jpg
  11. ^ http://www.ornl.gov/sci/techresources/Human_Genome/project/info.shtml#how
  12. ^ http://www.ornl.gov/sci/techresources/Human_Genome/faq/faqs1.shtml
  13. ^ http://www.ornl.gov/sci/techresources/Human_Genome/faq/faqs1.shtml
  14. ^ http://www.ornl.gov/sci/techresources/Human_Genome/faq/faqs1.shtml
  15. ^ http://www.ornl.gov/sci/techresources/Human_Genome/faq/faqs1.shtml
  16. ^ http://www.ornl.gov/sci/techresources/Human_Genome/hg5yp/
  17. ^ http://www.ornl.gov/sci/techresources/Human_Genome/faq/seqfacts.shtml#whose
  18. ^ http://www.ornl.gov/sci/techresources/Human_Genome/project/info.shtml#how
  19. ^ http://en.wikipedia.org/wiki/Human_Genome_Project
  20. ^ http://www.ornl.gov/sci/techresources/Human_Genome/elsi/elsi.shtml
  21. ^ http://www.ornl.gov/sci/techresources/Human_Genome/project/benefits.shtml
  22. ^ http://www.ornl.gov/sci/techresources/Human_Genome/project/benefits.shtml