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The Human Genome Project

Term Paper 2012 12 Pages

Biology - Miscellaneous

Excerpt

"For the genetically superior, success is easier to attain but is by no mean guaranteed. After all, there is no gene for fate. And when for one reason or another, a member of the elit falls on hard times, their genetic identity becomes a valued commodity for the unscrupulous." [1]

— Vincent Freeman, character in the movie Gattaca.

In the movie Gattaca, a future is depicted where parents may design the genetic equipment of their offspring prenatally. Since not everyone has access to this technology, individuals without genetical enhancement are considered “in-valids”. Although it is illegal to discriminate on the basis of genes, profiling a person’s genotype is common and used to qualify for employment. While only the “valids” are allowed to climb the social ladder, the invalids, considered more susceptible to disease and a shorter lifespan, are relegated [1, 2].[2]

Gattaca warns of the problems that arise if humans are reduced to nothing more than their genes, an ideology called genetic determinism. In the movie, the society generally accepts genetic determinism, culminating in the view that a genetic read-out acts as unchangeable prophecy, as predestination [3].

How likely is such a future, where one’s chances in life are restricted by his or her genetic code?

Among other scientists, Francis Collins, the director of the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) in the United States, attended a screening of the film [3]. Knowing the "science fiction buzz" about human genetics was important to him and should also be for other researchers in the Human Genome Project (HGP) [3].

And he knew what he was talking about: already years before the movie, the HGP has been source of similar ethical concerns as in Gattaca.

"The problem [with genetic research] is, we're just starting down this path, feeling our way in the dark. We have a small lantern in the form of a gene, but the lantern doesn't penetrate more than a couple of hundred feet. We don't know whether we're going to encounter chasms, rock walls or mountain ranges along the way. We don't even know how long thepath is. ”[4]

— Francis S. Collins, director of the American NIH and the HGP (1990).

Starting in 1986 as a Human Genome Initiative by Charles DeLisi of the United States Department of Energy (DOE), the project received its final boost in 1988 by the enthusiastic effort of James Watson, predecessor of Francis Collins as head of the NHGRI [5]. Eventually, the HGP was founded in 1990 as DOE/NIH joint-project with funding of about $200 million a year and was expected to take 15 years [5].

Today, the achievements of the HGP can be seen as outstanding; it created an infrastructure for biology and medicine [6]. But then, the idea of sequencing the entire 3 billion bases of the human genome was discounted as “absurd”, “dangerous” and “impossible” by numerous critics [5]. And they were not that wrong: in 1990, the technology for whole genome sequencing was just not available. Therefore, sequencing the genome was postponed in the HGP until better technology has been developed that would make it faster and cheaper. To ensure that these technologies were soon available, some large-scale sequencing projects were funded by the HGP [6].

The first goal of the HGP was to construct high resolution linkage maps of polymorphic markers of the human chromosomes [6]. By linkage analysis, the arrangement of genes on the chromosomes can be determined upon co-inheritance of polymorphic DNA markers, but it provides now way to actually locate the genes on the chromosomes. Thus, physical maps of overlapping cDNA fragments covering the whole genome were build concurrently to eventually locate the markers from the linkage map on the DNA. Thereby, the identification of disease genes was made easier [6].

Besides, another focus of the HGP was to analyze and ultimately sequence the genomes of simple model organisms like the bacteria Escherichia coli (E. coli), the fly Drosophila melanogaster or the mouse Mus musculus [6]. This was done for several reasons: first, even if one day a possible disease gene has been encoded, the function of the resulting protein cannot be deduced just from its amino-acid sequence only [6]. But since evolution has been quite conserved between different organisms, a human gene might have its homologue gene in a model organism which allows figuring out that gene’s function much more easily. Second, learning to sequence the best is easier on a smaller genome of a model organism than on the large human genome [5].

But as the first real “big-science” project, the HGP also terrified the scientific community to a certain extent: people feared that on the one hand, money was pushed away from smaller projects and on the other hand, the creativity and freedom of individual researchers were dramatically reduced by this targeted and highly organized effort. For the HGP founders, it was just that the need for more coordination and organization in the project was exceeding what people were accustomed to [6]. To drop these arguments, the HGP early tried to maximize the public benefit by making available new tools to the scientific community and the release of new data before publication [7].

Apart from the sequence data and genomic as well as physical maps of the human genome, the project also produced some rather surprising findings. First, the genome sequence between different people is almost identical - 99.9% of the nucleotide bases are the same. Second, less than 2% of the genome encodes for proteins. And third, the total number of genes, previously estimated at 80,000 to 140,000, is only around 23,000. Unfortunately, the function of more than the half of them is yet unknown [8].

In addition, the HGP’s key goals also included addressing the ethical, legal, and social issues (ELSI) that may arise from the project. Therefore since its inception, 3% to 5% of the annual HGP budget was devoted to study the implications of the rapidly increasing knowledge about the human genome and the technological progress in this field on individuals and society. Thereby, the HGP ELSI program represents the world’s largest bioethical program. Among other issues, ELSI topics include: fairness in the use of genetic information, privacy and confidentiality, commercialization of products as well as psychological impact and stigmatization [9].

In the following, I will present the most challenging ELSI topics. Some of them are not directly related to the HGP, but definitively emerge from the increasing the availability of genetic information to which the project immensely contributed.

"We used to think our fate was in our stars. Now we know, in large measure, our fate is in our genes." [10]

— James Watson, Nobel prize winner for the discovery of the DNA structure (1989).

"Each individual is entitled to lead a life in which genetic characteristics will not be the basis of unjust discrimination or unfair or inhuman treatment." [11]

— Human Genetics Commission (2002).

In Gattaca, a genetic read-out after birth determines the destiny of the main character Vincent: with predispositions for mental disorders and heart failure as well as a reduced life expectancy, he is a victim of genetic discrimination right from the start [2]. Although “it’s illegal to discriminate on the basis of genetics -genoism it’s called- [...]” [1]. Vincent seizes the only chance to avoid genetic discrimination by “borrowing” the genetic profile of an injured star athlete [2]. This is just a movie, but how real is such a genetic discrimination nowadays?

Basis of this concern is always a genetic test, by which a person's DNA - taken from cells in a sample of blood or, occasionally, from other body fluids or tissues - is examined for some anomaly that represents a disease or disorder. This anomaly may be large, like a missing or additional peace of a chromosome, or small like a missing, additional or alternated nucleotide base. For instance, genetic testing is used to confirm suspected DNA mutations responsible for a certain phenotype or to look for a possible predisposition for a disease. Today, around 1,000 genetic tests are available [12].

I think many people are still believing that genetic discrimination is more science-fiction than reality, but in the United States, cases have already been reported where employers used findings from genetic tests to avoid recruiting candidates that were shown to possess genes associated with susceptibilities for diseases that are expensive, interminable or incurable [13]. Besides employers, people are afraid that also insurance companies might take use of genetic information to calculate the risk of developing certain diseases for their candidates. As result, individuals with high risk status might be totally excluded, have reduced coverage or pay astronomically high contributions for a health or life insurance.

To counter this development, a law called GINA became effective in 2008 in the United States [13]. This “Genetic Information Nondiscrimination Act” prohibits American insurers and employers “from discriminating on the basis of information derivedfrom genetic tests ” and additionally, they are not allowed to demand a genetic test [13]. This is a first step, but still it remains to be generally declared who should have access to personal genetic information and who not, to prevent the misuse of that sensitive information. In my opinion, this knowledge is highly confidential.

So if genetic information may influence an employer or an insurer for the choice in their candidates, how could it affect an individual itself? Suppose a genetic test results in a very high probability for a yet incurable disorder like Huntington’s disease, what would be your reaction? How would you behave? How would you continue living you life? No one can answer these questions without having been in this situation himself. And the fact that genetic testing most often only provides a probability and not a certainty makes life not easier. Some people who carry a disease-associated mutation never develop the disease.

Besides, another issue would be how to keep that information private; how to avoid the people around you from noticing it? Genetic information is highly confidential, and once it becomes public, it implicates a high risk of stigmatization, even if the changes are not visible at first glance. Thereby the society’s perception of the affected individual would change, even if most people would certainly argue against it.

Not only after birth or as adult, genetic testing is available also prenatal. Pre-implantation genetic diagnosis (PGD), also known as embryo screening, allows for instance prenatal sex discernment and may therefore be used to select embryos in one sex preferentially. One may use it to screen for a specific genetic disease; it is available for many monogenic disorders such as cystic fibrosis or Huntington’s disease. Especially for pregnant women of advanced age, PGD is used as a screening for chromosomal abnormalities in the embryo and thereby may increase the rate of pregnancy success, as in this case pregnancy loss due to aneuploidy is a frequent problem [14] [15]. Recently, it has been published that even whole genome sequencing of the embryo from blood samples of pregnant women is possible [16].

“Designing babies” may be an option of PGD as well, including for example the modification of physical characteristics of the unborn child by changing its genetic composition [17]. This may be one step towards eugenics as in Gattaca and raises several questions: is modifying the genetic code for non-therapeutic reasons ethically justifiable? Should “imperfect” embryos or ones with gene defects be aborted? Or would such a practice even be legally allowed in the future?

In Germany, PGD is generally prohibited, but since the end of 2011, it is allowed if a severe genetic disorder in the child or miscarriage is possible due to the genetic predisposition of the parents [18] .

Currently there are no regulations for evaluating the accuracy, reliability and utility of genetic tests [9], so one cannot definitively know if they are safe and the results trustable. Some genetic tests were developed in pubic laboratories, while others are marked by companies as kits that can be purchased by everybody [9]. This is critical since certainly not everybody is able to interpret the results or will engage genetic counseling. A lot of education for the handling of genetic information is hence necessary, especially for healthcare personal [9].

[...]


1. Gattaca, 1997. Niccol, A., DVD, 106 min, USA: Columbia Pictures.

2. Wikipedia, the free encyclopedia, Gattaca, 2012. http://en.wikipedia.org/wiki/Gattaca (2012/07/15).

3. Kirby, D.A., The New Eugenics in Cinema: Genetic Determinism and Gene Therapy in GATTACA, 2000. http://www.depauw.edu/sfs/essays/gattaca.htm (2012/07/15).

4. Nash, M.J., Tracking Down Killer Genes. TIME Magazine, 1990/09/17.

5. Roberts, L., The human genome. Controversial from the start. Science, 2001. 291(5507): p. 1182-8.

6. Mapping the Genome: The Vision, the Science, the Implementation. Los Alamos Science. 20: p. 68-93.

7. Collins, F.S., Morgan, M., and Patrinos, A., The Human Genome Project: lessons from large-scale biology. Science, 2003. 300(5617): p. 286-90.

8. U.S. Department of Energy Office of Science, Insights Learned from the Human DNA Sequence, 2009. http://www.ornl.gov/sci/techresources/Human_Genome/project/journals/insights.shtml (2012/07/15).

9. U.S. Department of Energy Office of Science, Ethical, Legal, and Social Issues, 2011. http://www.ornl.gov/sci/techresources/Human_Genome/elsi/elsi.shtml (2012/07/15).

10. Jaroff, L., The Gene Hunt. TIME Magazine, 1989/03/20.

11. Human Genetics Commission, Inside Information: Recommandations, 2002. http://www.google.de/url?sa=t&rct=j&q=each%20individual%20is%20entitled%20to%20le ad%20a%20life%20in%20which%20genetic%20characteristics%20will%20not%20be%20t he%20basis%20of%20unjust%20discrimination%20or%20unfair%20or%20inhuman%20tre atment.&source=web&cd=6&ved=0CGEQFjAF&url=http%3A%2F%2Fwww.hgc.gov.uk% 2FUploadDocs%2FContents%2FDocuments%2Fiirecommendations.pdf&ei=QL8CUNH_L 4XptQaLuP3ZBg&usg=AFQjCNGyZfjZQDRdIFi_zT_IIgXzWglxtA&cad=rja (2012/07/15).

12. U.S. Department of Health and Human Services, Understanding Gene Testing, http://www.accessexcellence.org/AE/AEPC/NIH/index.php (2012/07/15).

13. U.S. Department of Energy Office of Science, Genetics Privacy and Legislation, 2008. http://www.ornl.gov/sci/techresources/Human_Genome/elsi/legislat.shtml

14. Reproductive Genetics Institute, What is PGD, 2011. http://www.reproductivegenetics.com/pgd.html (2012/07/15).

15. U.S. Department of Energy Office of Science, Gene Testing, 2010. http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetest.shtml (2012/07/15).

16. Kitzman, J.O., et al., Noninvasive whole-genome sequencing of a human fetus. Sci Transl Med, 2012. 4(137): p. 137ra76.

17. Future Human Evolution, Genetic Engineering, 2010. http://www.humansfuture.org/genetic_engineering_designer_babies.php.htm (2012/07/15).

18. ZEIT online, Bundestag erlaubt Embryonenauswahl im Labor, 2011. http://www.zeit.de/wissen/2011-07/pid-bundestag-entscheidung (2012/07/15).

Details

Pages
12
Year
2012
ISBN (eBook)
9783656313250
ISBN (Book)
9783656314684
File size
553 KB
Language
English
Catalog Number
v204136
Institution / College
University of Ulm
Grade
1,0
Tags
human genome project

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Title: The Human Genome Project