Human Genome Project: Legal, Ethical and Social Implications

serviceman Genome Project Legal, Ethical and Social ImplicationsIn this dissertation we accomplishment out the homoeity genome sound projection in its wider context. We take a brief overview of the aims, the working and the sequencing techniques practiced unitedly with the timeline achieved.The ability to charm factors has given a capitaler judgement of the serviceman genome. This understanding has thrown up a great m each heavy, social medical and ethical problems and predicaments which clearly fatality tube both communicate and solved. This dissertation looks at many of the issues, dismembers them, and considers any(prenominal) of the possible solutions.We primarily consider the situation in the UK, but comparisons atomic number 18 drawn with the arguably more battleful society in the USA, particularly in friendliness of the legal implications of the subject.We make a consideration of the ethical position of researchers, medical professionals and also indivi duals whether they atomic number 18 considered as research subjects or simply as private citizens.We draw conclusions from our findings and present them.IntroductionThe Human Genome Project (HGP) was a vast and ambitious c at ane timept which was conceived in the 1980s and family eithery started in 1990, the of import stated aim of which was to achieve the mapping of the entire human genome. It was lordly anticipated that the process would take just roughly 15 years and was in that locationfore scheduled to be complete in2005/6 but the advances in technological hard and softw be improved sequencing ability to the tip that the entire undertaking was actually completed in 2003.The project itself involved over 1,000 principal scientists in over 200Universities, Government laboratories and private facilities.The stated and delineate primary inclinations of the project were toidentify all the approximately 20,000-25,000 factors in human desoxyribonucleic acid,determine the s uccessivenesss of the 3 billion chemical stolid pairs that make up human DNA,store this knowledge in databases,improve in additionls for data analysis,transfer related technologies to the private sector, andaddress the ethical, legal, and social issues that whitethorn arise from the project.(after Collins FS et al 1998),Although the project was primarily about the sequencing of the human genome, part of the intrinsic preparatory work was carried out in the sequencing techniques of other organisms such as E Coli and Drosophila(the fruit fly) brief description of the genomeThe genome of an organism is a term which relates to the sum total of the DNA of the organism. This is replicated in virtually every cell in the organism and it should be remark that it includes non only the nuclear DNA but the extra-nuclear DNA as well. It is the basic code for making all of the constituent proteins and in that locationby it is the ultimate causal factor of the various processes that occu r within the organism. The human genome has approximately 3 billion base pairs (abbreviated as A T G C).These argon arranged in sequential style in the DNA double helix and are unique to an individual. in that location are large areas of repetition and large areas which appear to be biologically silent but we shall discuss this in rather greater detail later in this dissertation. (Nichols, E.K. 1998)Sequencing techniques usedThe scourtual age derived in the human genome project does not somebodyify anyone individuals genome. The original samples were taken from multiple spermatozoan and blood (from females) donations which were mixed and sent to labs across the world. The differences were comparatively peanut as the vast studyity (99.7+%) of the genomic sequence is identical in ever soy individual.(Collins et al 2001)Sperm is used, as the DNA protein ratio is higher in sperm than for other cells and is in that locationof easier to prepare. It should be scard that sperm c ontains both the male and female sex chromosomes (X Y) so equal numbers of each were added to the samples and the blood DNA was added to ensure that female derived DNA was also present.The original sequencing techniques (in the 1990s) were primarily those of gel electrophoresis, which is slow, labour intensive and expensive. It was reported that the entire human genome project team managed to sequence 200Mb of gene in 1998. Advances in technology and automotive processing allowed one participant (DOE Joint genome institute) to sequence 1.5 billion bases in one month in January 2003. (Soga, Kakazuet al 2004)It was the discovery and large-scale implementation of the capillary gel electrophoresis technique that was mainly responsible for these advances. One of the major advantages of the capillary tube mode is that the comparatively larger surface area of the capillary tube allows for greater heat dissipation which was the rate limiting step for the older models as too much heat woul d melt the gel carrier. (Tsai et al.2004)The actual mechanism for sequencing is extremely composite plant but in essence each chromosome, which comprises between 50 and 250 trillion base pairs, is fragmented into more manageable size pieces. (the sub cloning step).Each piece is then set up as a template from which a set of smaller fragments are generated, each one is a base pair shorter than the parent (the template preparation and sequencing reaction steps). (Marsha et al 2004)The resulting fragments are stray by electrophoresis which is an ideal method because of their differing size (separation step). The end base of each fragment is then identified (base-calling step). Automated sequencers then sack analyse the resulting patterns which bequeath give representation of the base order which is then reassembled into blocks of about 500 bases each (for ease of handling the data) . Number of very sophisticated computing device programmes then analyse the raw data for potential e rrors and tramp identify specific genes and silent areas (Krill P et al 2000) at one time sequenced, the final details are placed in the public domain such as Embank for open access to all.We induce made several references to the draft and final sequences. The ac tallying of the difference lies in the fact that there are both intrinsic errors in the processing and also in the variability of the inheritable material used. The original draft sequence was published in June 2000. This was the result of each area organism analysed at least 4-5times to minimise the errors. This original data was presented inspections of about 10,000 base pairs and the chromosomal locations of the genes were known at this stage.A higher quality final reference sequence was published in April 2003which represented a 8-9 fold sequencing of every chromosome to interest in gaps and to minimise errors which were quoted as being no more than one in 10,000 bases (Kaiser et al 2004)Human genome project timeli ne1990 Official commencement of HGP workApr. 1998 HGP passes sequencing midpointMarch 1999 Target completion date for Human genome Working Draft accelerated to early 2000Dec 1999 Human Chromosome 22 sequenced (first human chromosome ever sequenced)May 2000 Human Chromosome 21 sequencedMarch 2000 Drosophila genome completedApril 2000 Draft sequences of Human Chromosome 5, 16 19 completedJune 2000 Working draft of DNA sequence achievedDec 2001 Human Chromosome 20 sequencedDec 2002 Complete Mouse genome draft publicationJan 2003 Human Chromosome 14 sequencedJune 2003 Human Chromosome Y sequencedJuly 2003 Human Chromosome 7 sequencedOct 2003 Human Chromosome 6 sequencedMarch 2004 Human Chromosome 13 19 sequencedMay 2004 Human Chromosome 9 10 sequencedSept 2004 Human Chromosome 5 sequencedOct 2004 Human gene count estimates changed from 20,000 to 25,000Dec 2004 Human Chromosome 16 sequencedMarch 2004 Human Chromosome X sequencedApril 2005 Human Chromosome 2 4 sequencedLegal issuesPat entingThe whole issue of patenting the genome and the offshoots of the project caused an enormous furor in medical, scientific and pharmaceutical circles. The opposing ends of the spectrum argued that, on the one hand, the benefits of such a fundamentally important piece of work should be freely acquirable for the human race in general and the scientific community in particular, to the other who believed that the money to be made by the commercialised exploitation of the genome could be used to finance other related projects. (Nuffield 2002)The culmination of the job was that the genome was fragmented and patented piecemeal. In order to fully understand the implications of this we must explore the whole kit and boodle of the patent system. In the UK, patents are issued by the Patent Office. Applications must be received within 18 months of the discovery (it is 3 years in the USA). Once granted, they remain in force for 20 years from the date of issue. In order to be considered s uitable for a patent to be issued a production must generally satisfy four criteria, namelyUseful the patent industriousness must be accompanied by some practical application of the invention (whether it has actually been applied or has been proposed in a purely theoretical sense)Novel it must be a new, or previously unusual entity.Non-obvious it must be a significant modification that is not simply a minor adjustment made by someone with remove attainment and training in that particular areaDetailed the item must be described in sufficient detail to allow person who has appropriate training in the field to use it for the purpose for which it was designed. This is very much referred to as the enablement criterion( after Cochran and Cox. 1997)The academic argument referred to earlier was intensified by the companionship that raw products of nature are not generally patentable. Special provision had to be made by the agencies on both sides of the Atlantic to allow for patent s to be issued for genetic material.The general guiding principal in publish patents is that they are issued on a first to invent basis.Where a specific application is not immediately obvious (as is the case with many pharmaceutical and bio-tech products), provisional patents can be applied for and enforced for up to one year after either discovery or publication of the findings. This is a mechanism to allow for the full implications of the finding to be worked out and patented.(Nickols F 2004)In specific reference to our considerations here, we should note that with bio-tech discoveries in general and DNA patents in particular, coincident with the application for a patent, the applicant is take to deposit a sample of their discovery in any one of 26 designated biological culture repositories which are distributed throughout the world. (Bjorn tad DJ, et al. 2002)It is a reflection of both the scale and importance of this work to appreciate that to date, there study been over 3 mi llion separate genome-related applications for patents received on file throughout the world.The legal ramifications of this process are huge. In the UK, USA and lacquer (where the bulk of the applications for genome-related patents are filed) the system requires that the details of the applications are kept completely confidential until the full patent is finally issued. As we name discussed, this process can take up to a year. (Brown,2000)The corollary of this fact is that those scientists and companies who utilise the data ( which is available on the Internet) to evaluate clinical or pharmaceutical applications of gene sequences risk the outlet of a future injunction if it transpires that those particular sequences have been the subject of a previous patent application which has afterward turned out to be successful. (Morris AH 2002)The 3 million genome related patents include the genes themselves, gene fragments, tests for specific genes, various proteins and stem cells.To s atisfy the Patent Office the four tests set out above are specifically modified to accommodate genetic material thus(1) identify novel genetic sequences,(2) specify the sequences product,(3) specify how the product functions in nature i.e., its use(4) enable one skilled in the field to use the sequence for its stated purpose(after Caulfield 2003)Even this is not completely sufficient for the current necessarily of science. If we take the example of gene fragments. Their function is often not known although their structure almost invariably is. The practical applications can be extremely vague. A quoted utility of a gene fragment has been cited as providing a scientific probe to help find another gene. Clearly it could cause important practical difficulties if a patent were to be issued on such a basis, and the subsequent usage was found to be substantially different, it would not invalidate the patent.The meaning of this can be fully appreciated if we consider that the typical ge ne fragment, comprising about 500 bases (known as expressed sequence tags or ESTs) actually represent typically about20-30% of the active chromosomal genetic material, the full chromosome may be about 40-60 times larger than this. The active chromosomal genetic material is often referred to as canal and typically only contains its information-rich (or exon) regions. The scientific importance of these gene segments are that they represent very useful tools for research as they can reduplicate the actions of genes, can be synthesised in the laboratory, and remove the need for scientists to manipulate the entire gene. (HUGO 2000)It can therefore be clearly be appreciated that such gene fragments are very useful tools in genetic research and the granting of patents touch entities has sparked off another major controversy in the scientific community. There have been major representations to the various Patent Offices throughout the world not to grant such patents to these universally im portant entities to applicants who have neither determined the base sequence of the genes nor yet determined their function and possible uses.As a result of this, the UK and USA Patent Offices decided to issue more stringent guidelines (effective as from 2001) which required that an application for patent of a gene fragment must now specifically state how the fragment functions before a patent can be issued. The wording is specific and substantial utility that is credible, but is still considered by many to be too indeterminate. (Thompson 1992)The basis tush the objections stem from the two main arguments already put forward. Firstly the patenting of such a bottleneck or gatekeeper product can seriously hinder the eventual development or even the characterisation of more complex molecules. Secondly, scientists are obviously wary of utilising such entities because of the possible financial constraints and penalties that would be imposed if the particular entity that they were using subsequently was found to bathe subject of a provisional (and therefore initially secret) patent application. In essence the patent of the gene fragment could be taken out after a comparatively small amount of scientific work and exert totally disproportionate control over the possible commercial and scientific development of more advanced genome research. (Schwarz D teal 1997),There are also less obvious, but very practical, implications to this type of patenting. Let us consider the situation where patents have been separately applied for, and granted to gene fragments, the gene and various proteins that the gene expresses. Any scientist wishing to-do research in that area has not only to pay the various license holders for permission to use their patented entity, but there are also hidden be in the research necessary to determine where (and whether)the patents have been granted. (Short ell SM et al 1998),Not all research has been hampered or driven by the restrictive practices t hat the issuing of patents inevitably promotes. Let us consider the case of the Welcome Foundation who, in collaboration with ten other smaller pharmaceutical concerns, agreed to form a non-profitmaking consortium whose stated goal was to find and map out an initial300,000 common single nucleotide polymorphisms (SNPs).To date they have discovered nearly 2 million. In a truly philanthropic gesture they generated a publicly available SNP map of the human genome in which they patented every SNP found all for the purpose of preventing others from making financial profit from them and making the information available to the public domain.The SNP is a single wavering in the base sequence in the genome and they are found, on average, about one in every 500 base units. It can occur in an active or in a non-coding region. The effect will clearly vary depending upon the actual site of the discrepancy but they are believed to be a fundamental cause of genetic variation which could give rese archers important clues into the genetic basis of distemper process or variations in responsiveness to pharmaceuticals. (Russell SJ1997)In addition it is believed that SNPs are responsible for variations in the mode that humans respond to a multitude of potential pathogens and toxins. The SNP is therefore an invaluable tool in the research behind multifactorial disease process where complex environmental and genetic interactions are responsible for the overall phenotypic expression of the clinical disease state. (Santis,G et al 1994).We have referred in passing to the arguments that are shortly raging relating to the issues on patenting genetic material. We should therefore consider the question of why patent at all? Would we be better off if the patent offices did not accept patents of genetic material?On first examination of the situation one might think that scientific investigation, in general terms, might slip by faster if all scientists had unlimited and free access to all information in the public domain. More careful consideration suggests however, the law of natures relating to intellectual property are built on the assumption that unless ownership and commercial profits can be reasonably secure (by means such as patents) few organisations would be willing to make the substantial investment that is typically necessary for development and research.The reasoning behind the mechanism of patenting intellectual property is therefore the marrying together of the need to secure a potential income from ones work with the ability to allow the transparency of full publication of ones discoveries which will therefore allow others to consider and utilise the information in their own research. (Berwick. 1996)Consideration of this point will suggest that the only other effective means of safeguarding the be of ones research would be total secrecy which clearly would not be in the general interest of the scientific community. If we add to the general thrust of this argument, the fact that, in general terms, the costs of development(post-invention) far outweigh the costs of research (pre-invention) we can see the economic sense in allowing in advance(p) research-based firms the financial security of development by preserving the profit incentives by means of the Patent. (DGP 2002)In general terms we could view the patent mechanism as a confirmatory development.(McGregor D 1965). Perhaps it is the breadth and number of the patents allowed in the field of genomic research that is the prime cause of unease in the scientific community.Special casesThe arguments presented above can be broadened further if one of the natural extensions of the human genome project is the research into the possibility of cloning. We will not consider the (currently totally illegal) possibility of human cloning per se, but the therapeutic embryo cloning for the purposes of harvesting human stem cells. Such cells have immense potential for the study and therapy of a great number of disease process. As such they have enormous value as both intellectual and commercial property.The background to our discussion here includes consideration of the fact that courts in both the UK and the USA (Diamond v. Chakrabarty1980) have set precedents that single celled organisms (genetically modified bacteria) were intrinsically patentable. Legal argument then followed and shortly after there were similar rulings in favour of the patentability of simian stem cells.It logically follows that human stem cells should be afforded the same legal protection. The problem arises then that such a move would offend other legal principles such as technical ownership of another human being.(PGA 2001) Clearly there are enormous, and some would check out insurmountable, difficulties in this region. We present this point simply to illustrate the potential difficulties surrounding ownership of the human genome.Broader legal issuesMatters relating to the legal implications ar ising from the human genome project already fill countless volumes and we do not propose to make an exhaustive examination of the subject. There are however, number of major issues that arise either directly or indirectly from this project. They are largely interlinked with major social and ethical considerations and society, as a whole, has looked to the law to provide authoritative answers to some of them. (Stripling R et al.1992)One of the major problems associated with the potential ability to decipher the human genome is what to do with the information that it gives us. The ability to read genes brings with it the ability to discriminate with increasing degrees of subtlety. Discrimination is inevitably linked (historically, at least) with varying degrees of injustice.Whether it is the more obvious forms of discrimination such as insurance loading on the basis of predisposition to disease traits or more seductive and pernicious scenarios such as the ability to discriminate by g enetic association with various ethnic groups, the ability is there. Will it become acceptable to hold out a mortgage application on the grounds that a person has been found to have a genetic disposition towards gastric cancer? Could wellness insurance premiums be based on an interpretation of various aspects of ones genome?Some lawyers have already voiced their concerns about the ability of the law to provide genetic defences where it may be possible to challenge prosecutions on the ability to undermine the ethical principle of the validity of individual responsibility. The concept of free-will may be legally challenged in the prospect of discovery of various genetic traits that may predispose the individual to any one oaf number of conduct patterns such as antisocial or thrill-seeking behaviour or violence. (Laurie G 2004)We currently accept that some manifestations of the human genome are now routinely enshrined in virtually unchallengeable law. DNA identification in criminal la w is commonplace and scarcely questioned. Paternity suits are settled on the basis of genetic make-up. It doesnt take a quantum leap of intuition to appreciate that there may curtly be potential negligence cases brought against physicians and the like who fail to caution patients against the possibility of developing the ever increasing number of disease processes that are thought to have a genetic predisposition or component.The converse of that dilemma is should we expect physicians to suppress information found by genetic testing if there is no known cure? It follows that if we do not then sight could be condemned to live with the knowledge that they are statistically belike to develop any one oaf number of diseases that they may very well, in other circumstances, have chosen to live in ignorance of. (Hyde, SC et al. 1993)Such cases have already surfaced, unsurprisingly in the USA. The estate of a colonic cancer victim unsuccessfully tried to sue a physician who failed to war n him about a genetic predisposition to colonic cancer from which he subsequently died. (Safer v land of Peck 1996)Some measures have been taken to try to protect exploitation of the genetic status of individuals where it is known. In the USA, some 16states have enacted laws to prevent both health and other insurance companies from using any form of genetic information to load premiums or to refuse cover.The initial reaction to these moves was one of delight, but it soon became clear that this was only of any potential value when the individual was asymptomatic. There was no bar to premium levels once the symptoms became apparent. To some extent, although the same level of legal prohibition does not apply in the UK, there is little difference. In this country, insurance companies will still load premiums or refuse cover once symptoms are apparent. (Rothstein MR1999)Social and medical considerationsAs we have implied earlier in this piece, the fundamental nature and importance of t he human genome project to humanity as a whole means that its impact has great implications for the handle of law, ethics and social considerations. This is hardly surprising as, at the most basic level, all these three considerations are inextricably linked.Many of the social implications are also tied up with medical considerations and therefore we shall consider both of these elements together.Humans, as a race, have about 3 million pairs of bases that determine their genetic identity. Interpersonal differences between individual humans however, are determined by only one tenth of one present of our collective DNA. These three million base pairs are ultimately responsible for the physical and perhaps behavioural diversity that we observe in our species. (Erickson 1993)It is in the nature of inheritance that this variation has accumulated across the generations by small mutations or variations in the base sequences. These small differences are ultimately responsible for all human diversity including many overt disease process and predisposition or resistance to others.It is clearly important where these mutations take place as some have no functional effect, others may confer some form of advantage or benefit (and thereby the motive factor behind the evolutionary processes) others may cause disease or even be incompatible with life.(Griesenbach U et al 2002),It can be argued that all disease process have at least a genetic component. It can be completely due to a genetic malfunction such as the defect in the single gene for the cystic fibrosis transmembraneconductance regulator (CFTR) which results in an abnormal expression of one protein (the protein is still expressed, but due to one amino acid impairment it folds in a different way) which results in the clinical situation of cystic fibrosis. (Piteous DJ et al 1997). Equally it may be due to a variation in the genetic code that modifies how the immune system responds to a particular pathogen (Yoshimura, K et al. 1992).As we understand how our genome influences literally every aspect of our health we will inevitably discover more ways to combat and tackle the diseases of mankind. Before we move on to discuss overtly social and ethical considerations we should logically elicit the appraisal and examination of the medical issues, as they have a pronounced bearing on these other areas.With the advent of a greater understanding of the human genome and the cellular mechanisms of regulation and disease comes the prospect of gene therapy. On the one hand, the potential benefits for the sufferers of single gene mutation syndromes such as Tay Aschs disease and Sickle Cell Anaemia are clear and undisputed, and yet the same technology has enormous social and ethical ramifications.There are thought to be about 4,000 single gene defect syndromes known to medical science at present (Termite, S et al 1998). These are the prime targets for the gene therapy researchers There are also an enormous nu mber of more complex, but still primarily genetically determined disease process, such as Alzheimers Disease and schizophrenia, together with the commoner Diabetes Mellitus and hypertension variants which, although having a genetic component, are thought to be manifested after a period of interaction with environmental factors. It is quite possible that the techniques of gene therapy could ultimately be applied to these conditions as well.(Sikorski R et al 1998),Social and medical benefitsThe advent of understanding of gene function leads to other developments in the fields of both diagnostics and possibly preventative medicine. There is already considerable debate in pharmaceutical circles about the ability of researchers to utilise genetic information to make predictive assumptions about the ability of individuals to metabolise drugs. (Sailor R et al. 1998).One of the big problems with pharmacology is that, although a normal response to a particular drug can be predicted reasonabl y accurately, there are variations in genetic make-up which cause marked differences in threat of metabolism and excretion of some drugs. In many cases, these differences are of minor clinical importance, but in anaesthetic and cytotoxic drugs, the differences can be lethal. (Wriggle DJ 2004).As extension of this thread of argument is that it is known that some malignancies will respond well to some cytotoxic agents while others will show no response at all. The point behind these comments is that there are considerable efforts in the pharmaceutical industry to identify the particular regions of the genome which are ultimately responsible for these differences. If they can be found it follows that they may either be capable of modification (by gene therapy or other mechanism) or their effect can be measured so that the dose (or even the type) of medication can be adjusted with far more confidence in the knowledge of the likely pharmacodynamics of that individual patient.(Spindle et al 2002). It is the ultimate hope and goal of these efforts that the pharmaceutical industry will ultimately be able to speed up the process of drug development, make the drugs faster and more effective while dramatically reducing the number of adverse drug reactions observed.Social and medical difficultiesGene tests are currently in the process of being developed as a direct result of the human genome project. Some are already commercially available. the social implications here are huge. Quite apart from the medical implications of being able to predict the likelihood of possibly developing certain disease processes, there are legal and social applications as well. Courts have been presented with the results of gene tests in cases as diverse as medical malpractice, privacy violations, criminal cases and even child custody battles.(Diamond. B. 2001)The immediate difficulty in this area is, firstly that there is insufficient knowledge to be able to interpret the results of the gene tests with 100% accuracy. This, when combined with the knowledge that many of the conditions that currently can be tested for have no known or successful treatment, leads to enormous social and ethical dilemmas.While it may be considered quite reasonable to tell a person that they are carrying a defective gene for cystic fibrosis ( as a carrier state, rather than a symptomatic individual) and thereby allow them to make positive decisions with regard to whether they choose to run the risk of passing that particular gene on to future generations. Is it reasonable to tell someone in their 20s that they are likely to develop Alzheimers Disease in their 60s? How will that knowledge impinge upon their approach to life? (Douglas C 2002)Equally how will such knowledge impinge on the eventual application and acceptance of health insurance policies which are currently worked out on