Human Genome Project: Legal, Ethical and Social Implications

compassionate Genome Project Legal, Ethical and loving ImplicationsIn this dissertation we get word the world genome project in its wider context. We walk out a brief overview of the aims, the working and the sequencing techniques apply together with the timeline compassd.The office to successiveness ingredients has minded(p) a greater visualizeing of the man genome. This understanding has thr feature up a great m whatso of all time levelheaded, affable medical and ethical problems and dilemmas which clear invite tube both(prenominal) addressed and solved. This dissertation looks at m either of the slues, analyses them, and considers some of the practicable solutions.We primarily consider the situation in the UK, all when comparisons argon drawn with the arguably much litigious society in the USA, pointly in regard of the legal implications of the subject.We bushel a consideration of the ethical position of assimilatekers, medical professionals and as wel l individuals whether they ar considered as search subjects or simply as private citizens.We draw conclusions from our findings and fork up them. cosmosThe valet Genome Project (HGP) was a sizeable and ambitious concept which was conceived in the 1980s and form bothy started in 1990, the main stated aim of which was to achieve the functionping of the whole forgivingkind genome. It was originally anticipated that the functioning would take approximately 15 years and was whence scheduled to be staring(a) in2005/6 save the advances in technological hard and softw ar improve sequencing baron to the extent that the entire undertaking was rattling completed in 2003.The project itself involved over 1,000 read/write head scientists in over 200Universities, regime laboratories and private facilities.The stated and defined primary cultures of the project were toidentify all the approximately 20,000-25,000 factors in gracious desoxyribonucleic acid,determine the propagat ion of the 3 billion chemic chemical group pits that make up human DNA,store this teaching in data fundaments,improve tools for data analysis,transfer tie in technologies to the private sector, andaddress the ethical, legal, and hearty issues that whitethorn arise from the project.(after Collins FS et al 1998),Although the project was primarily well-nigh the sequencing of the human genome, part of the intrinsic preparatory work was carried out in the sequencing techniques of other(a)(a)wise organisms much(prenominal) as E Coli and drosophila(the fruit fly)Brief comment of the genomeThe genome of an organism is a term which relates to the sum fit of the DNA of the organism. This is replicated in virtually e very cell in the organism and it should be say that it includes non only the nuclear DNA further the extra-nuclear DNA as well. It is the basic write in code for making all of the constituent proteins and thereby it is the last determinant of the various moti no np beils that evanesce 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 take over helix and are unique to an individual. on that point are large playing areas of repetition and large areas which appear to be biologically silent but we shall discourse this in rather greater detail later in this dissertation. (Nichols, E.K. 1998)Sequencing techniques customdThe eventual sequence derived in the human genome project does not array each(prenominal) unrivalled individuals genome. The original samples were taken from multiple sperm and product line (from pistillates) donations which were mixed and sent to labs across the realism. The differences were comparatively insignifi abidet as the vast major(ip)ity (99.7+%) of the genomic sequence is identical in all individual.(Collins et al 2001) sperm cell is used, as the DNA protein ratio is higher in sperm than for other ce lls and is therefore easier to prepare. It should be noted that sperm contains both the male and female sex chromosomes (X Y) so equal issuances 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 jelly 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 process allowed matchless participant (DOE Joint genome institute) to sequence 1.5 billion bases in one month in January 2003. (Soga, Kakazuet al 2004)It was the see to ity and large-scale implementation of the capillary gel electrophoresis technique that was mainly responsible for these advances. one and only(a) of the major gains of the capillary tube method is that the comparatively larger surface area of the capillary tube allows for greate r heat dissipation which was the rate close step for the older models as too much heat would endure the gel carrier. (Tsai et al.2004)The actual mechanism for sequencing is extremely complex but in essence each chromosome, which comprises between 50 and 250 zillion base pairs, is staccato into more manageable size pieces. (the sub cloning step).Each piece is whence rophy up as a template from which a set of depresseder severs 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 separates are uninvolved by electrophoresis which is an ideal method because of their differing size (separation step). The end base of each fragment is thus identified (base-calling step). Automated sequencers hence loafer analyse the resulting patterns which volition commit representation of the base order which is then reassembled into blocks of near 500 bases each (for ease of handling the data) . Number of very sophisticated computer programmes then analyse the raw data for electric strength errors and can identify particularized genes and silent areas (Krill P et al 2000) once sequenced, the final details are placed in the public cranial orbit such as Embank for open access to all.We stir make several credits to the draft and final sequences. The explanation of the difference lies in the point that there are both intrinsic errors in the processing and also in the vari skill of the transmitted material used. The original draft sequence was published in June 2000. This was the result of each area universe analysed at least 4-5times to minimise the errors. This original data was presented inspections of near 10,000 base pairs and the chromosomal locations of the genes were k instantern at this stage.A higher quality final reference sequence was published in April 2003which represented a 8-9 fold sequencing of every chromosome to fill in gaps and to minimise e rrors which were quoted as being no more than one in 10,000 bases (Kaiser et al 2004) kind genome project timeline1990 Official spring of HGP workApr. 1998 HGP passes sequencing midpointMarch 1999 Target completion date for compassionate genome running(a) Draft accelerated to early 2000celestial latitude 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 sequenced common people 2004 Human Chromosome 5 sequencedOct 2004 Human gene count estimates changed from 20,00 0 to 25,000Dec 2004 Human Chromosome 16 sequencedMarch 2004 Human Chromosome X sequencedApril 2005 Human Chromosome 2 4 sequencedLegal issues visibleingThe whole issue of patenting the genome and the offshoots of the project caused an wondrous furore in medical, scientific and pharmaceutical circles. The opposing ends of the spectrum argued that, on the one hand, the benefits of such a cardinally important piece of work should be freely accessible for the human race in ecumenic and the scientific community in particular, to the other who believed that the money to be made by the commercial ontogeny of the genome could be used to finance other related projects. (Nuffield 2002)The culmination of the transmission line was that the genome was fragmented and patent piecemeal. In order to richly understand the implications of this we essential explore the workings of the patent system. In the UK, patents are issued by the visible Office. Applications essential be original with in 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 suitable for a patent to be issued a product must primarily run into four criteria, namelyUseful the patent operation must be accompanied by some practical activity of the hammerion (whether it has actually been applied or has been proposed in a purely theoretical sense) fable it must be a new, or previously un cognise entity.Non-obvious it must be a significant modification that is not simply a minor adjustment made by someone with appropriate cleverness and training in that particular areaDetailed the item must be described in sufficient detail to allow soul who has appropriate training in the field to use it for the purpose for which it was designed. This is much referred to as the enablement criterion( after Cochran and Cox. 1997)The academic argument referred to earlier was intensify by the companionship that ra w 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 patents to be issued for hereditary material.The general guiding principal in issue patents is that they are issued on a first to invent basis.Where a specific application is not straightawayly obvious (as is the exemplar with many pharmaceutical and bio-tech products), provisional patents can be applied for and implement 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 patent.(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 required to deposit a sample of their discovery in any one of 26 designated biological culture repositories which are distributed through out the world. (Bjorn tincture DJ, et al. 2002)It is a reflection of both the scale and importance of this work to esteem that to date, there stick out been over 3 million 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 Japan (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 defecate discussed, this process can take up to a year. (Brown,2000)The corollary of this accompaniment 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 issuing of a future prohibition if it transpires that those particular sequences dedicate been the subject of a previous patent application which has subsequently 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 satisfy the Patent Office the four tests set out above are specifically modified to accommodate genetic material thus(1) identify original 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 accredited needs 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 substantial practical difficulties if a patent were to be issued on suc h a basis, and the subsequent usage was found to be substantially different, it would not invalidate the patent.The significance of this can be fully appreciated if we consider that the typical gene fragment, comprising about 500 bases (known as expressed sequence tags or ESTs) actually represent typically about20-30% of the supple 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 learning-rich (or exon) regions. The scientific importance of these gene segments are that they represent very useful tools for seek as they can ingeminate 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 a nother major controversy in the scientific community. There open been major representations to the various Patent Offices throughout the world not to grant such patents to these universally important entities to applicants who have neither determined the base sequence of the genes nor insofar determined their function and possible uses.As a result of this, the UK and USA Patent Offices decided to issue more stringent guidelines ( hard-hitting 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 behind the objections stem from the two main arguments already put forward. Firstly the patenting of such a bottleneck or doorkeeper product can seriously hinder the eventual exploitation or even the characterisation of more complex molecules. Secondly, scientists are obviously awake of utilising such entities because of the possible financial constraints and penalties that would be imposed if the particular entity that they were development subsequently was found to bathe subject of a provisional (and therefore signly 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 hold back over the possible commercial and scientific development of more ripe(p) 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 costs in the research necessary to determine where (and whether)the patents have been granted. (Short ell SM et al 1998), non all research has been hampered or driven by the restrictive practices that the issuing of patents inevitably promotes. Let us consider the case of the Welcome pedestal who, in collaboration with ten other smaller pharmaceutical concerns, concur to form a non- remunerationmaking consortium whose stated goal was to find and map out an initial300,000 common single nucleotide polymorphisms (SNPs).To date they have ascertained nearly 2 million. In a truly philanthropic apparent motion they generated a publicly available SNP map of the human genome in which they patented every SNP found solely 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 revolution in the base sequence in the genome and they are found, on average, about one in ever y 500 base units. It can occur in an active or in a non-coding region. The resultant depart clearly vary depending upon the actual site of the summercater but they are believed to be a fundamental cause of genetic variation which could give researchers important clues into the genetic basis of ailment process or variations in responsiveness to pharmaceuticals. (Russell SJ1997)In addition it is believed that SNPs are responsible for variations in the itinerary that humans suffice to a multitude of potential pathogens and toxins. The SNP is therefore an priceless tool in the research behind multifactorial malady process where complex environmental and genetic interactions are responsible for the overall phenotypical expression of the clinical disease state. (Santis,G et al 1994).We have referred in spillage to the arguments that are currently raging relating to the issues on patenting genetic material. We should therefore consider the question of why patent at all? Would we be mend 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 hurt, might proceed faster if all scientists had innumerable and free access to all information in the public domain. much careful consideration suggests however, the laws relating to intellectual property are built on the assumption that unless ownership and commercial profits can be more or less secure (by means such as patents) few organisations would be impulsive to make the substantial investment that is typically necessary for development and research.The view 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 king to allow the transparency of full publication of ones discoveries which entrust therefore allow others to consider and utilise the information in their own research. (Berwick. 1996)Con sideration of this point leave alone suggest that the only other legal means of safeguarding the costs of ones research would be total secrecy which clearly would not be in the general following 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 innovative 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 positive development.(McGregor D 1965). Perhaps it is the breadth and subprogram of the patents allowed in the field of genomic research that is the flower 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 go forth 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 tidings 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 say 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 arising from the human genome project already fill limitless 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 mixer and ethical considerations and society, as a whole, has looked to the law to stand 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 insidious and pernicious scenarios such as the ability to discriminate by genetic association with various ethnic groups, the ability is there. Will it become acceptable to refuse a mortgage application on the grounds that a person has been found to have a genetic disposition towards gastric cancer? Could health insurance bounteousnesss be based on an interpretation of various aspects of ones genome? almost 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 behaviour 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 law is commonplace and scarcely questioned. Paternity suits are colonized on the basis of genetic make-up. It doesnt take a quantum fountain of intuition to appreciate that there may soon be potential negligence cases brought against physicians and the like who fail to warn 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 smash information found by genetic testing if there is no known cure? It follows that if we do not then people could be condemned to live with the knowledge that they are statistically likely to develop any one oaf number of diseases th at 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 warn him about a genetic predisposition to colonic cancer from which he subsequently died. (Safer v Estate of Peck 1996) roughly measures have been taken to sweat 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 the human genome project to humanity as a whole means that its impact has great implications for the fields of law, ethics and social considerations. This is hardly surprising as, at the most basic level, all these common chord considerations are inextricably linked.Many of the social implications are also fix 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 last responsible for the physical and perhaps behavioural diverseness 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 subway 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 inconsistent 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 ami no acid irregularity 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 extend the appraisal and examination of the medical issues, as they have a pronounced way 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 te chnology 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 number 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 goal 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 perhaps preventative medicine. There is already considerable debate in pharmaceutical circles about the ability of resear chers to utilise genetic information to make predictive assumptions about the ability of individuals to metabolise medicines. (Sailor R et al. 1998).One of the plentiful problems with pharmacology is that, although a normal response to a particular drug can be predicted reasonably accurately, there are variations in genetic make-up which cause marked differences in threat of metabolism and reasoning by elimination 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 follow s 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 hotfoot 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. rather 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 p resented 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. spot 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 affect the eventual application and acceptance of health insurance policies which are currently worked out on