HIE 289A The Impact of Science and Technology on Society and the Environment Royal Military College of Canada

The Impact of Genetic research on Society from a Scientific, Medical and Ethical Perspective

Submitted by: 25475 OCdt Saroop, KDA Instructor: Major Bertram Frandsen Date: 28 November 2011

While writing papers very few history students contemplate the complexity of the computer they are writing on. The keyboard they use to input their commands are combined with their gestures performed by their mice in order to get a co-ordinated signal which directs their computer to perform a task. These computers are run by complex coding which comprise millions of lines of code, from 60 million lines on Windows 7 to 86 million lines code on MAC OS X. If these codes were printed they would comprise over 20 000 pages and weigh in at 200lbs and occupies roughly 4 Gb1, yet an equivalent amount of code is printed billions of times over in the human body weighs virtually nothing and occupies roughly 830 mB or less2 than 25% of Windows 7. This coding still powers a system of systems infinitely more complex than even the most powerful super computers running all over the world. Decoding this sequence, of DNA, also took humans much more time to do, and will take society even longer to understand. In 1990 a group of scientists led by Ari Patrinos, director of the Office of Biological and Environmental Sciences Division of the US Department of Energy formed the National Institutes of Health National Human Genome Research Institute, commonly known as the Human Genome Project. The Human Genome Project (HGP) is an international body which strove to determine the sequencing of the Human Genome, or the 23 000 genetic base pairs composed of three billion nucleotides that form the human genetic makeup and directs everything from eye colour to afflicting Down Syndrome on children. The project, completed

"How Many Lines of Code in Windows?"

Field, Hyman. "Public understanding of science versus public understanding of research."

in 2003, at a cost of $3 billion USD3, has opened huge possibilities to the world. With the sequencing of Deoxyribonucleic Acid (DNA) came the ability of researchers to dissect it more rapidly than dreamed possible in 1953, 50 years earlier, when Watson and Crick published their first findings on the basis of DNA and the pairs constituted in it. With this rapid dissection came increased examination, rapid sharing of discoveries and advancing knowledge. This advancing knowledge while having the potential to cure diseases and increase human performance to previously unattainable levels through DNA manipulation, the ramifications of these actions on society as we know it could be massive given the large ethical, legal and social issues that encompass such bold advancements in the field of Human Genetics. The Human Genome is the collection of DNA that drives our basic functions and identities. It is stored primarily on 23 chromosomal pairs comprising 46 unique chromosomes with a small amount stored in the core of mitochondria, the component of the cell responsible for producing energy. The haploid human genome, the type found in all cells not responsible for sexual reproduction, contains 23 000 genes, comprised of 3.3 billion DNA base pairs3. These base pairs are made of 4 types of nitrogen based proteins; adenine, thymine, guanine and cytosine; with adenine combining with thymine and guanine combining with cytosine in order to create the core DNA double helix found in all genes. These double helixes then fold in on themselves, using hydrogen bonds, to form complex secondary and tertiary structures which add to the complexity and variety of the 46 unique chromosomes. Of the 23 chromosomal pairs, 22 of them are responsible for all non-sex-linked characteristics, while the

Roach; Boysen, C; Wang, K; Hood, L (1995)

final chromosome decides all sex-linked characteristics, which other than the obvious manifestations such as shorter stature for females, more muscle mass in males and differing sex organs also contributes greatly to differing rates of genetic diseases which are carried on the X chromosome and are therefore more prevalent in either sex depending on where in the chromosome they are located. Surprisingly, despite the complexity of the system required and the already compact nature of DNA, it is actually composed almost entirely of junk DNA or DNA which the scientific community has yet to discover any use for other than providing place holding information4. This DNA continues to mystify scientists as it violates all laws of nature where excess is removed for improved efficiency over millennia. This junk DNA also increases the already substantial risk of DNA mutation which while beneficial on a gross scale, by evolving species, causes horrible diseases and organ failures in people on an individual basis. In order to sequence this vast amount of information advanced biological technology (bio tech) must be used in order to be able to sequence the entire DNA chain within a lifetime5. Partial sequencing is also used extensively in diagnostic tests to determine if an illness has a genetic basis. It is also used in biotechnology, in sequencing dangerous infectious diseases and in forensic biology as commonly seen in crime scene dramas. The first method of sequencing was developed by Walter Fiers by 1976 and is still used today in high schools4. This method termed the chain terminator method, took DNA, broke it into many small DNA fragments and

4 5

J. Gustafson, Genomics of disease pg 131-132 Kreuzer, Helen. Biology and biotechnology: science, applications, and issues. Pg 88-97

mixed them into a slurry6. This slurry was then ran them through an agar gel which was electrified, giving a positive and negative pole. This polarization caused the DNA fragments to move in either direction in a predictable pattern given their order, which would allow the slurry to develop into a ladder pattern showing the individual genes. This method, while functional, could take days to process a single gene, and gave large errors without alerting the scientist as to the potential of error6. This means that the tests would have to be run numerous times in order to ensure accuracy, and even then it would have to be run under different conditions by different scientists so that a systematic error could be ruled out. This was a highly demanding process for each new gene to be added to the Human Genome Project s data bank, making it so that it could take up to a month for a single gene to be added. This complexity with regards to gene processing led to the contemporary method known as Polymerase Chain Reaction (PCR)6. PCR was developed to a point at which it could be used for research in 1993, 10 years after its initial introduction and 3 years into the HGP. PCR s introduction to the field of genetic research increased the rate at which DNA sequencing ran exponentially. PCR uses thermal cycling which heats and cools the DNA in order to facilitate DNA melting and enzyme replication to create millions of copies of the DNA. These heating and cooling cycles require precise timings mechanisms so that the DNA is cracked in the right locations and is the replicated to the right length. DNA primers are pieces of DNA which are not part of the sample being analysed but which are like blank CDs, and allow the copy of the DNA sequence onto itself. The process works by unzipping the DNA helix at a high temperature, usually above 90C, for 30 seconds which causes the DNA helixes to melt. The
6

Bartlett, J. M. S.; Stirling, D. (2003)

temperature is them dropped to 50C for 20 seconds which allows the primer to anneal to the single stranded DNA template. The solution is then heated up to 80C, just below the temperature at which the DNA would melt. At this stage the polymerase, for which the method is named, is at its optimum temperature and copies the sample DNA onto the primer. The temperature is then dropped to 10C, re-zipping the original helix which is facilitated by removing energy from the system, causing the helix to close in on itself, creating two DNA fragments where there was only one. It is thus apparent that as PCR continues the rate of replication also increases so that DNA may be analyzed from very small samples, as few as a 3 cells, although the larger the sample the more accurate the results. After 40 cycles, enough DNA is created to run the DNA through an agar gel like in the chain termination method. While PCR is quick, it would still take decades to sequence the entire genome; therefore scientists developed High-Throughput Sequencing in order to produce millions of sequences at once whereas PCR created one sequence at a time. This allows the sequencing of DNA to occur in the matter of hours, a far cry from where the project began. Using current technology it is now possible to rapidly and accurately recreate and sequence the Human Genome in order for scientists to analyze the DNA of any individual and develop a genetic map, which is then used to determine a myriad of factors about that person6. The Human Genome Project is one of the most important projects to humanity for a variety of reasons, in addition to all the applications of the genome, there are also aspects of the project which have added to the bulk of humanity s knowledge on a variety of topics. From the technology used to sequence DNA, to the discoveries that came from its sequencing,

and the additional questions that have arose from it, the Human Genome Project has exploded the horizons of science which is clear evidence of its use to society. In order to sequence any genome, be it as complex as an Adders-Tongue Fern with 1260 diploid chromosomes, or as a simple as an ant with 2 chromosomes, the same general procedures are used7. In order to sequence the human genetic code though with its 46 diploid chromosomes, it was necessary to develop the methods for sequencing. While it is possible to sequence genes using the chain termination method developed in 1976, this method is quite laborious taking days to work and was quite inaccurate6. PCR was thus developed in order to expedite the sequencing process with more accurate results delivered faster in a very precise and controlled method which could be recreated indefinitely as long as the machine was calibrated, a process not at all time consuming given the time saved. By sequencing the DNA fragments that were produced from the PCR method, and then finding out which genes coded to produce which proteins, it was possible to understand the denaturing of proteins, and why this occurred8. Since protein synthesis is essential to all known life forms on the planet, knowledge of what causes it, drove research into why it fails. This research is yielding promising results in order to use gene manipulation in order to not only cure cancer but identify it before it occurs. It is possible that gene manipulation may then be capable of reversing the cancerous growth by controlling the rate at which proteins are synthesized in undesirable cells and then have them slow down their replication, allowing oncologists to control the disease progression. If this results yields the results it lends itself to, then it is very

7 8

Mark Hon Fong, Medical cytogenetics pg 334-382 "Gene Therapy for Cancer: Questions and Answers" August 31 2006

possible that the cure to cancer would not have been possible without the sequencing of the human genome8. Sequencing the human genome is not in any way technically different than sequencing any other form of DNA. This has resulted in a mass expansion of sequencing effort on animals since the completion of the HGP. The technology that was developed for the HGP as well as the technical expertise and lessons learned have also added to the rate at which animal DNA can be, and is sequenced. This mass influx of knowledge has taken the veterinary community by storm and has driven research into the links between human and animal diseases, how they are linked and how they can both be cured9. Research is also being conducted on the links between humans and the animal kingdom in order to strengthen the evidence in favour of evolution. By providing evidence beyond the current casual links, scientists would be able to trace humanity s lineage more adequately, both as a whole, as well as through individual genealogy. This would allow historians and archeologist to better recreate migration routes of early humans to trace culture and genetic tracts that were once forgotten. In addition to the purely academic uses this would have, it may also explain the linking of traits across races, explain how humans evolve and may even identify the missing link between humans and Great Apes that explains our origins. It is without debate that finding this missing link would be of a huge benefit to society9. By sequencing the human genome, scientists have been able to see which proteins were created from which amino acids. It has long been established that the ability for an

Carlson, Robert H., 1970 pg 110-118

environment to support the growth of amino acids is a fundamental requirement for life to occur. Using this knowledge and combining it with knowledge gleaned from space exploration it becomes readily apparent that scientists may be able to combine the knowledge of which amino acids are essential to life and which planets support those essential amino acids10. This would allow scientists to create a map of the known universe detailing which planets would be able to support which levels of complexity of life. This would help scientists to know which planets they should direct their search for extraterrestrial life on in order to maximum their search efforts. In addition to speeding up the search for life, Stephan Hawking postulates that the knowledge of which planets could support life, and their distances to us, would be invaluable in protecting earth from extraterrestrial life forms. He says that any extraterrestrial life would most likely not be out to aid humanity, and therefore knowledge of where it could be growing would be invaluable in order to protect ourselves from it and that indirectly, from sequencing the human genome, it is possible that we could get an advanced warning about where an attack against humanity might come from10. By understanding the genetic makeup common to all humans, scientists may be able to effectively answer a question that has plagued educational psychologists for decades, are the majority of traits innate or learnt, or in other words, solve the nature vs nurture debate. By determining which genes affect our intelligence, it would be possible to determine which genes should be turned on or off in order to produce smarter humans, or cure learning

10

Beech, Martin, Of All Things Visible and Invisible The Physics of Invisibility

disabilities5. It would also allow more efficient education to occur that would be targeted to an individual, not based on years of observation, but based on hard facts about their potential, abilities and their known advantages which would in theory create a much more efficient educational system, saving potentially billions of dollars in wasted resources5. This system would more importantly though, create the potential to rapidly educate the masses and have a larger educated workforce, something which has been recognized as being a sure way to advance society rapidly, which would be of definite benefit to it. While most scientists would have laymen believe that all their research is interesting, it usually is not, though there are rare nuggets which are interesting to the world over. One of these discoveries was made after sequencing the human genome and realizing that whereas scientists had originally thought that a human s 46 chromosomes had the genetic material for 2 million unique genes they discovered that there are in fact about 23 000 genes, or almost 1% of the anticipated amount6. The rest of the genetic material is coined junk DNA and what the rest of this DNA is, is still a mystery to science. Some scientists speculate that it is there for redundancy while others suggest that within this genetic material there is a map work of where humanity has evolved from, also linking to the missing link between humans and apes. This junk DNA is found in all species which deepens the intrigue, as it is not a unique event, but carries statistical significance. What science can agree on though, is that nature streamlines everything, so that if this DNA is there, it has some purpose that is improving survival rates amongst species. This common junk DNA is also the basis of the links between species as humans are differentiated from other species by very very small amounts of genetic material,

on the order of 1%, that indicates that this common junk DNA does have a purpose. While this DNA is not understood it is the basis of future research, and by getting scientists to ask more questions, it is pushing our knowledge of humanity and our interaction with our environment further. There are strong links developed between the implications of mapping the human genome on science as well as medicine. The clear difference between the two is that while scientific pursuits expands the body of knowledge, medical pursuits expand the scope of care that can be provided to patients. Mapping the human genome had some large implications on human medicine. From improving cancer treatments to understanding the spread of virulent diseases and predicting genetic diseases, mapping the human genome is one of those giant leaps forward that occur every 30 years or so in medicine that redefines what is possible, and changes the course of treatment for the next century. It would be impossible to examine all the future applications of mapping the genome on medicine since new methods are being discovered daily but some of the most exciting developments with immediate applications are cancer treatments and detection, disease research and genetic counselling, three areas which individually could alleviate mass suffering, but when combined could change the face of medicine. Cancer research has always been heavily funded given that is could strike anyone anywhere and was thus one of the the most equally funded research in the last decade when compared against socio-economic class8. It has always been a matter of when the cure would emerge, and not if a cure would emerge, and with the development of gene therapy, this is

even closer now than before. With gene therapy it will soon be possible to detect cancer earlier, thus increasing cancer detection, and starting treatment sooner. More promising is the research into treatments. Currently, using retroviruses, or engineered viruses, scientists are able to inject different genetic material in cancer cells11. If this genetic material could be genes that either restrict the growth of blood cells or stop the replication of cancerous cells, doctors would have effectively cured cancer. Further into the future, doctors are looking at improving the body s detection of cancerous growths and killing them sooner before they become out of control. Finally, the most promising of all treatment research is the least radical, changing cancer cells so that they are more receptive to radiological treatment. Under this system genes would be inserted directly into the tumour that makes them weaker when exposed to radioactivity such are chemotherapy11. This would increase the speed at which cancers are treated by increasing chemotherapy s effectiveness11. As can be seen, in both the short and long term, genetic therapies that were derived from the HGP are changing the way cancers are detected and treated, which impacts a large portion of society. Disease research involving genomics covers a wide range of topics since genetic manipulation seems to be the new silver bullet since penicillin. The research into virulent diseases looks to be the most interesting, with advances being made against HIV, AIDS and Influenza. With HIV and AIDS, the virus causing these enters the host s cell and rapidly multiplies killing off the host s immune system until any amount of bacteria or germs will kill them. The HIV-AIDS virus rapidly evolves undergoing many mutations per reproductive cycle

11

("Gene Therapy for Diseases" )

making it difficult for doctors to isolate and research. With mapping the human genome, technology now exists to rapidly map how the HIV-AIDS virus is evolving, so that better methods can be used to control it11. Additionally, treatment methods are being developed that either attempt to change the genetic composition of the virus so that it is no longer harmful and the immune system can dispose of it, or directly destroying the virus by ramping up the body s immune system, by inducing a short term form of auto immune disease against the host cells that house the virus11. These methods also apply directly Influenza where scientists are trying to stop the rapid mutations which occur and limit the diseases effectiveness. While relatively harmless to middle aged individuals in the developed world, Influenza is devastating to the young and old in developed countries and everyone in underdeveloped countries12. Eliminating Influenza, which is not just the flu but also includes viruses such as H1N1 and SARS, would potentially save thousands of people a year and save the medical system millions a year in Canada alone12. It is evident that through genetic research made possible by mapping the human genome, research is being conducted that could change the face of disease research. Perhaps one of the most controversial medical treatments is the use of genetic counselling. This involves either parents being advised of potential complications for their children, or individuals learning about their increased risk for certain diseases due to their genes13. Doctors can advise patients whether to abort a fetus because it contains the required genes for Huntington s Disease or the child will have developmental problems11. This can add undue stress onto the family or individual, but is also potentially a huge tool for parents. If
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World Health Organization, "Genetics of Influenza."

("Gene Therapy")

they know they are not in a position to care for such a child, they would be able to make a decision that is both best for the child and for the family unit as a whole. With individuals it allows them to seek treatment earlier and monitor their health more precisely and gives their family doctor indications as to where this person s health is heading. Once these genetic deficiencies are discovered, they also open up new treatment options which are only available before symptoms start to present such as with Alzheimer s14. This could potentially improve the quality of life for millions of people across the world and extend the lives of others by increasing the effectiveness of the treatment11. Research that has surfaced since the human genome was mapped is improving the lives of people today and will continue to do so in the foreseeable future as more tests and treatments are discovered for individuals afflicted by all diseases. The ethical dilemmas that doctors face today are not trivial. In their hands lies people s health and lives, and an enormous amount of trust is vested in them. This responsibility only grows when medicine ventures out into genetic research as society may not be ready to deal with all the ethical legal and social issues that will arise from the implementation of research derived from mapping the human genome. One of the primary concerns with genetic testing involves the data that can be gleaned from such tests. Someone s entire medical history may be seen from a few fragments of DNA15. This information is shed daily through discarded skin cells and hair follicles which can easily be collected without people s knowledge. This has huge legal and social implication

14

Fletcher, Joseph "Ethical Aspects of Genetic Controls

Designed Genetic Changes in Man." Pg 62-73

15

Government of Canada. Ethics in Research Board.

since people do not even know this data is being collected from them. Additionally, people who are forced to submit to such tests such as military members and prisoners with blood tests have no assurances that their information will not be used in conducting scientific trials9. The current system of law in the west has not yet dealt with these questions and it is up to the lawmakers in each country where this technology is emerging to address these issues in a manner compatible with that regions cultural values. Another question of concern regards the abortion of fetuses when the child may have a higher risk of disease or developmental issues14. Doctors argue that they have the responsibility to inform parents of the health concerns of their child, and if abortion is legal in the region, then it should be allowed. Doctors also argue that they should use all information available in order to advise parents about family planning so that if the parents cannot handle future issues with their children, it would be possible for families to take alternative measures to start a family such as adoption. Interest groups argue that since this technology was not available 20 years ago, it must be tightly maintained by government agencies so that it can slowly be introduced into societies and will not shock society into making rash decisions they would otherwise not have made14. Additionally, opponents argue that the potential for designer babies exist, or babies that have their characteristics chosen before insemination. This would remove a large part of the genetic diversity that stops many genetic diseases from rapidly replicating throughout populations14. This can be seen in many closed communities such as the Ashkenazi Jews which had developed without external genetic material for almost a
millennium and thus have a higher prevalence of genetic diseases14. Again law makers and medical

ethics boards must convene in order to ensure that these amazing technologies are available

to those who need it, and that the patients are provided with all required information to ensure they make informed choices that are again compatible with the values of the region. Finally, with the 2012 Olympics approaching, it is apparent that sports enhancements are becoming a larger problem for international sporting bodies. From this stems the question involving the greater population, of if there is an acceptable amount of enhancements that can occur before someone is no longer considered a natural human9. While many of these enhancements have legitimate medical purposes, such as growing muscle tissue for people suffering from muscular dystrophy, they can also be abused by individuals who are looking to enhance their performance illegally9. While this is a legitimate concern, it is in no way different from what occurs with the use of pain killers which can be used either for good or for bad. It is up to medical boards to maintain that technology is neutral and that the potential for abuse should not limit the potential good that could arise from its use. It is apparent from analysis that there are clear benefits which have arisen from mapping the Human Genome, but while these benefits cannot be discounted, there needs to be oversight and regulation to ensure that the technology is appropriately applied to society as a whole so that the greatest good can be extracted from the technology while limiting abuse. This conclusion is not unique to the human genome and its derivatives though, it is instead a common theme throughout all scientific pursuits and has a large application future engineers who need to understand that while they are changing the world in which we live for the greater, they must still keep the world livable and cannot lose sight of this balancing act.

Works Cited
1) "How Many Lines of Code in Windows?" Knowing.NET. December 6, 2005. 2) Field, Hyman. Public Understanding of Science (2010): n. page. Web. 16 Oct. 2011. http://pus.sagepub.com/content/10/4/421.short>. 3) Roach; Boysen, C; Wang, K; Hood, L (1995). "Pairwise end sequencing: a unified approach to genomic mapping and sequencing". Genomics 26 (2): 345 35 4) J. Gustafson, Genomics of disease, (New York: Springer, 2008), 5) Kreuzer, Helen. Biology and biotechnology: Science, Applications, and Issues. Washington, D.C. : ASM Press, c2005. 6) Bartlett, J. M. S.; Stirling, D. (2003). "A Short History of the Polymerase Chain Reaction". PCR Protocols. 226. pp. 3 6.

7) Mark Hon Fong, Medical cytogenetics, (CRC Press, 2000), 8) "Gene Therapy for Cancer: Questions and Answers" August 31 2006 National Institute of Health, "Gene Therapy for Cancer: Questions and Answers." Last modified August 31 2006. http://www.cancer.gov/cancertopics/factsheet/Therapy/gene. 9) Carlson, Robert H., 1970 Biology is Technology : The Promise, Peril, and New Business of Engineering Life. Cambridge, Mass: Harvard University Press, c2010.

10) Beech, Martin, Of All Things Visible and Invisible The Physics of Invisibility, (New York: Springer, 2010). 11) American Society of Gene and Cell Therapy, "Gene Therapy for Diseases." http://www.asgct.org/about_gene_therapy/diseases.php.

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World Health Organization, "Genetics of Influenza." Last modified March 2003. http://www.who.int/mediacentre/factsheets/2003/fs211/en/. US Department of Energy, "Gene Therapy." Last modified Aug 24 2011. http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml. Fletcher, Joseph. "Ethical Aspects of Genetic Controls - Designed Genetic Changes in Man." New England Journal of Medicine. (2001): 776-783. Web. 16 Oct. 2011. <http://www.nejm.org/doi/full/10.1056/NEJM197109302851405>. Government of Canada. Ethics in Research Board. Ethical Conduct for Research Involving Humans- Genetics. 2010. Web. <http://www.pre.ethics.gc.ca/eng/archives/tcps-eptc/section8-chapitre8/>.

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