Bioethics in India: Proceedings of the International Bioethics Workshop in Madras: Biomanagement of Biogeoresources, 16-19 Jan. 1997, University of Madras; Editors: Jayapaul Azariah, Hilda Azariah, & Darryl R.J. Macer, Copyright Eubios Ethics Institute 1997.

1. The Ethical Implications of the Human Genome Project and Human Genome Diversity Project
Darryl R.J. Macer

Institute of Biological Sciences, University of Tsukuba, Tsukuba Science City 305, JAPAN


The genome project is the collective name for genetic mapping and sequencing efforts being pursued in various organisms by scientists around the world. These projects, primarily the Human Genome Project (HGP), arose out of past decades of genetics research, and have resulted in knowledge of the complete genetic sequence of some bacteria and yeast, and will yield that of plants and animals including human beings. The data generated is being shared by researchers around the world, but the quantity involved requires advanced genetic and computing technology.

The benefits of this grand project of molecular genetics include the rapid and economical identification of disease-related genes, and the expansion of genetic diagnosis and therapy. There will be numerous benefits for agriculture and industry. However, there are numerous ethical, legal and social impact (ELSI) issues magnified by the enormity of the project. These include privacy and genetic testing, genetic discrimination, eugenics, and genetic determinism issues. The potential economic rewards of utilisation of the gene sequences has led to questions about patenting of cDNA and other genetic data, which are still to be resolved. There has already been a shift in society during the course of this project to focus on the genetic causes of phenotype, and this trend could result in ethical abuses of the information, as well as a different view of humanity. We need to examine the role of molecular and cellular genetics in medicine and society, and educate people how to utilise genetic knowledge for the physical, mental and spiritual health of all people.

A project to study the genome of many individuals and population groups is called the Human Genetic Diversity Project (HGDP). This raises a number of social and ethical issues including: Consent from individuals; Consent from population groups; How to obtain free and informed consent; Selection and participation; Use of the knowledge gained; Return of benefits to participants; Clash of world-views; Does the right not to know apply to communities?; Who speaks for a community?; Ownership of genes and derived knowledge; Public understanding and racism or eugenics; Stigmatization and genetic reductionism; International oversight of anthropologists & geneticists.

Population genetics is not simply a multiplication of the individual ethical and legal issues already raised by genetic research. There are different concerns and traditions in each group under study, and even among individuals within any group. The degree of information, consultation and cooperation must reflect such differences in participants. Likewise, the role and responsibilities of the researchers and of the local and national authorities, as well as the societal implications, will differ. For the future we need consultation with populations; individual and group consent mechanisms; ongoing ethical review; inclusion of representatives of populations in decision-making; communication, education, benefits, and feedback strategies at the population level; confidential data and sample banking; continual scientific review and monitoring; and appropriate sanctions. We also need to start gathering systematically the examples of use and abuse of DNA and cell sampling, to give us the necessary knowledge to better predict the future. Above all we need to have anthropologists and scientists who seek ethical sampling.

The Genome Projects

The genome project is an international project aimed at obtaining a detailed map and a complete DNA sequence of the genome of a variety organisms, including mycoplasma, bacteria, e.g. Escherichia coli (completed in 1997), the yeast Saccharomyces cerevisiae (completed in 1996), the roundworm Caenorhabditis elegans, the fruitfly Drosophila melanogaster, wheat, rice, the mouse and that of Homo sapiens. It is the Human Genome Project which has captured the public attention, and has been the image responsible for increased funding of genetics research since 1988-1990.

The number of human genes that have been sequenced is exponentially growing, and it is impossible to keep a count on the progress. The expected completion date of the project is around the year 2,000 A.D. and most gene sequences are already known. The countries involved in the HGP at the time of writing include Australia, Canada, China, The European Community (especially France, Germany and the UK), Japan, Russia, South Korea and the USA. Genetic analysis of a number of other organisms is also well underway as part of the Genome Project, and the common language of genetics and similarity of many genes means that molecular and cellular genetics is being advanced by studies on all organisms.

Origins of the Genome Project

There have been various accounts written of the origin of the Human Genome Project. The other Genome Projects arose in terminology at the same time or after the phrase "Human Genome Project" had been coined. However, all of these projects involve genetic mapping and sequencing which was underway long before the trendy phrase of "Genome Project" was used, and specific long term projects to entirely sequence some viruses, eucaryote organelle and bacterial genomes have been underway since the late 1970s.

Mapping of the human genome has been progressing for decades (Culliton, 1992). The beginnings of the genome project can be at least traced back to Mendel's genetic studies on peas, the mapping of the trait for colour blindness to the X-chromosome of Drosophila by T.H. Morgan and workers, to Avery and colleagues that found DNA was the physical substance of genes, to Crick, Franklin, Watson and Wilkins who determined the structure of DNA, to those who discovered the genetic code, to Sanger and others who developed DNA sequencing, and to many others who contributed to our knowledge of genetics and molecular biology. Therefore, no single person can claim to have initiated the goals of the genome project; and the date of the origin is obscure.

The progress in genetics since the 1960s has been rapid, and by the 1980s the goal of mapping and sequencing the complete genome of particular organisms became a distant goal. The first organisms to have their DNA sequenced were viruses, then the complete mitochondrial DNA of some organisms was sequenced. Projects in Europe, Japan and North America began which were aimed at automating DNA sequencers in preparation for the project. In scientific conferences in the 1980s people discused the idea of a human genome project. In 1988 the Polymerase Chain Reaction (PCR) was devised, which increased the rapidity of DNA manipulation enormously. By 1992 the project had resulted in physical genetic maps of human chromosomes 21 and Y, a refined complete genetic map of human DNA; and the complete sequence of a yeast chromosome.

The Genome Project has political dimensions as could be expected for any project requiring much funding, with the huge potential rewards for biotechnology industry from the sequencing and future application of genes to medicine and agriculture. The country putting forward the most money for the project is the USA, and some would say that the genome project as a specific image arose in the USA. There were several people in the USA who saw the goals of the genome project as ideal for initiating the first large scale biological research project with a definite endpoint (Cantor, 1990). The Human Genome Project or Human Genome Initiative is the collective name for several projects begun in the late 1980s in several countries, following the USA Department of Energy (DOE) decision to create an ordered set of DNA segments from known chromosomal locations, to develop new computational methods for analyzing genetic map and DNA sequence data, and to develop new techniques and instruments for detecting and analyzing DNA (OTA, 1988). The DOE has had a long term interest in assessing the effects of radiation on human health, and sequencing the genome may allow detection of mutations in the DNA. Whether the motive was to fill vacant DOE Laboratories; to provide renewed emphasis for science; or to put US biotechnology companies in a better international position (Lewin, 1990), the idea itself was sure to catch the imagination of politicians. Some biologists commented that they do not think physicists can do good biology, so the project should not be left to the DOE, and because the National Institutes of Health (NIH) is the major funder of U.S. biomedical research, the NIH joined the project. The activities of the NIH and DOE have been coordinated for genome research since they signed a Memorandum of Understanding on October 1, 1988.

The genome project is often compared to the Apollo space project. The analogy shows the glamour of the project. Not only will the genome project lead to the development of useful new technology, but unlike the Apollo project, the goal itself is also of immense direct practical use. The importance of the project initiation to reaching the goal is also different, people would not have gone to the moon if a positive decision had not been made, but the human genome map will be obtained, with or without a positive effort, though over a longer time scale if undirected (Macer, 1991). The original time frame was fifteen years, which has since been considerably shortened.

There have been numerous scientists who have contributed to our knowledge, and it will also be fitting that to complete this project will require the joint collaborate work of innumerous scientists, internationally. In the perspective of who initiated the project, who does the work, and whose knowledge is needed, the answer is clearly that many people are, and will be, directly responsible for the mapping and sequencing, and the later interpretation of the data.

Genetic Mapping

The DNA that is being sequenced is a composite of different human tissue cell lines. About 0.3-0.5% of the nucleotides in our DNA vary between different people. These differences vary from person to person, therefore it does not matter whose genome is actually sequenced. Different laboratories often use different human tissue culture cell lines, however, by the characterisation of standardised marker regions the DNA between different individuals will be able to be compared, and a single general map and sequence produced.

A detailed genetic map of the human genome was refined prior to full scale sequencing. A map is essential to efficient sequencing so that a physical library of DNA fragments can be systematically sequenced. The distance unit used in gene mapping is called a centi-Morgan (cM), and one cM is equivalent to two markers being separated from each other in chromosome crossing over in normal reproduction 1% of the time. The actual physical length of 1cM varies, being approximately 1 million base pairs (Mb) in humans.

The construction of any map requires markers. The markers of sequence are specific DNA sequences, and the longer the sequence the less copies there will be in any genome. A sequence of 20 nucleotides, for example, is generally unique in a genome. There are two types of maps, maps that are drawn in picture, and physical maps which include a physical collection of sequences of known order and location. Genome analysis involves both types. For short sequences, such as a few genes, convenient markers are the specific nucleotide sequences that are cut by restriction endonuclease enzymes. A sequence of DNA can be cut into smaller specific pieces by digestion with restriction enzymes, and the pattern from digestion with several different enzymes can be used to make a map of that sequence. The use of restriction fragment linkage patterns (RFLPs) in combination with genetic linkage analysis allowed the construction of linkage maps for each human chromosome with an average spacing of 10-15cM in 1987 (Doris-Keller et al., 1987).

The current mapping paradigm is based on a proposal in 1989 to use physical sequence-tagged sites (STS) as the map labels (Olsen et al., 1989). These sequences are longer than those utilised by restriction enzymes, and may be 100-1000 nucleotides long, so that a single tagged site in a genome can be defined by this short nucleotide sequence. Different researchers use different cloning vectors for gene analysis, so the exchange of DNA pieces in these different vectors, or DNA clones, is not possible. What is possible using the DNA polymerase chain reaction (PCR) is to generate DNA sequences for any DNA if short sequences are known for each STS, from which primers for the PCR can be made. Therefore, the ends of large DNA fragments should be sequenced, and the data combined to make a STS map of each chromosome. This approach means that researchers can continue to use different methods, and develop better procedures, while the information obtained can be integrated to progress the actual physical map. This will avoid the need to exchange different clones of DNA between laboratories, because each laboratory can use the marker sequence as a starting point. This approach was used to make maps of the human genome with decreasing average spacings XXX.

The initial approach was for different research groups to concentrate on different human chromosomes in order that they could all have the complete map in a shorter time. There are actually 24 chromosomes to be sequenced, 22 autosomes and the X and Y chromosomes. An initial goal is a map with STS markers spaced at about 100,000 base pairs, and the assembly of overlapping contiguous cloned sequences (called contigs) of about 2 million base pairs length. From this physical and informational library system, the sequencing was started. Data management technology must also improve, such as programmes to search the DNA sequence libraries, using advanced computing technology (Watts, 1990).

Physical chromosome maps (overlapping cloned pieces of the complete chromosome) are made by cloning overlapping pieces of DNA, and tags on each piece allow the pieces to be put into order. This means that once a disease-causing gene is localised to a particular region of the DNA, the appropriate clone can be taken from a freezer and sequenced. In 1992, researchers in France describe improved techniques which meant that a whole human genome approach, not individual chromosome approach, could be used to construct a physical library of contigs (Bellanne-Chantelot et al., 1992). A French project, Généthon, took the lead in genome mapping in 1992-3 because it was the world's largest gene mapping lab (Anderson, 1992a). They completed the first physical human genetic map in 1993, using automatic robotic analysis systems. The library of overlapping clones is basically completed using yeast artificial chromosomes (YACs). There are minor gaps where the DNA sequences are difficult to clone. Following its rapid progress the USA began setting up two large genome mapping centers, as the approach begun to be directed at the whole genome rather than just individual chromosomes.

Using the STS approach allows small teams of researchers to contribute results. There are worldwide efforts, although the major international effort is centred around the USA/Canada, Europe and Japan. There are many people from Australia, and Latin America who are also involved in work, via access to international DNA databanks. There will be contributions from many other countries for particular genome projects that have regional economic importance also, for example, China has a rice genome project.

Smaller genomes are useful models for the human genome, and several organisms are models for the sequencing project. The 5 Mb Escherichia coli and 15 Mb S. cerevisiae (yeast) sequences were major successes.XXX Yeast was the first eucaryote organism to have a fully sequenced genome. The first multicellular organism that is expected to be fully sequenced is the roundworm Caenorhabditis elegans. This genome project is being undertaken at the MRC Laboratory of Molecular Biology in Cambridge, U.K., and at Washington State University, USA, with other international collaborators. It is being used as a model project as a prelude to the sequencing of the human genome. The total sequence is about 100 Mb. This worm is one of the best characterised animals in the world, with the complete pattern of cell divisions for the whole organism (959 nuclei) and the full connections of the 302 nerve cells known. The life cycle is 3.5 days, which makes it easy to study mutations. The work on the physical map began in the early 1980s, and the genome is arranged in less than 50 contigs (pieces of contiguous cloned DNA sequence) (Coulson et al., 1991). In 1992 about 1 Mb of sequence was produced, and this figure is likely to increase to about 5 Mb of sequence in 1993. The cost of sequencing per nucleotide has fallen to about US 50 cents, a tenth of the cost in 1988 when the genome project began.

The model plant organism is Arabidopsis thaliana. Another model organism that has much historical significance to genetics is the fruitfly, Drosophila. The size of the D. melanogaster genome is estimated to be 165 Mb, with about 5-15,000 genes (Merriam et al., 1991). A physical cloned map has been completed, and the sequence may also be completed before the human sequence. Drosophila has been used in mutation studies of gene function for many decades, and because of a short generation time will continue to be a major research organism for genetics. The genetic sequencing will allow detailed genetic mutation studies at a nucleotide level, which allows studies of the affects of chemical mutagens and ionising radiation.

The mouse genome is the same size as that of humans, yet there is also a mouse genome project because of the use of mice in genetics research. Most of the mouse project is underway in the USA, and a 1 cM resolution genetic map is expected by 1995. There is much similarity between the mouse and human genomes, so the maps and sequence markers share many similarities. Cattle breeders have also begun a cow genome project, pig breeders a pig genome project, and behavioural geneticists have begun a dog genome mapping project to examine genes that are linked to the selected behavioural traits of inbred dog strains.

Genetic Sequencing

For many purposes there does not need to be any repository of DNA pieces, what is required is a computer data bank of the sequence. The project requires the establishment and constant improvement of databases containing the sequences of genes, and their location. There are several international databases, and the information should be openly shared among them to make the best and most up-to-date database possible. However, the physical cloned genes may be more efficiently obtained from cloned libraries, and such cloned libraries are becoming available from both the public and private sector. For example, the YAC contig library made at Généthon has been copied for several laboratories and is intended to be openly available to all peoples.

The total sequencing project for a genome of 3000 Mb will take a few years work by several large laboratories, however, by sequencing cDNA, which is complementary DNA to mRNA, was possible more quickly and cheaply. cDNA represents the expressed genes of a tissue or organism that the mRNA was obtained from. Short sequences of a few hundred nucleotides from a cDNA library were automatically sequenced by researchers in The Institute of Genomic Research (and others),, and these are called expressed sequence tags (ESTs). The sequences are tags because they can be used to identify a gene sequence, and as a probe from which the full gene can be cloned. In 1992 the US$70 million The Institute of Genomic Research (TIGR) was founded in the USA, which is directed by Dr C. Venter (Anderson, 1992b). The human cDNA sequencing was largely completed by 1994. The database was sold to Smith-Kline-Beecham, and had restricted access until April 1997 when it was made open to all. In the meantime others, especially Merck Inc. had obtained separate EST databases.


Biomedical research is performed and funded in many countries. For many years science has not only been the individual pursuit of people with unusual ideas, but rather it involves the funding of research by public or private money, consisting of taxes, charities and business investments. We should not be surprised therefore to hear the justifications for the funding of the project in terms of the business opportunities. The US Congress was partly convinced of the usefulness of funding the project by the opportunity to boost US biotechnology. However, in France, much of the money for the genome project comes from charity, which has different implications for the way that the data will be shared, as will be discussed later.

The U.S. portion of the project (possibly 50% of the total) was initially estimated to cost US$3 billion over the next 15 years, to the intended completion date in 2005 A.D. However, new technology suggests the date will be the year 2,000, and the cost may be cheaper. The total cost is unknown because the project is being broadened to include other organisms as models, private companies are also spending money, and many countries are contributing additional money to it. Data handling will be another important portion of the total. The 1992 government funding in the USA specifically for the human genome project (not including other indirect research on genetic mapping) was US$164 million (NIH US$105 million/DOE US$59 million). When one compares this with the cost of the development of a single drug, at US$100 million at that time (now US$300 million), or the annual U.S. health care expenditure of about trillion dollars, it is a small price to pay for such a large amount of information. Biotechnology is very big business, and the projected average US$200 million annually for the human genome project in the USA (National Research Council, 1988) is minor. The scientific methodology for sequencing DNA is routine, and the initial costs of US$1-5 for each nucleotide were reduced to 5 cents per base before the major sequencing effort began in 1996.

The initial fear of scientists was that the money would come from other biological research, which traditionally involves many small projects encouraging many individual scientists. Critics would prefer the project to stop after generating a general genetic map of the chromosomes, and after the cDNA had been sequenced. Identifying a particular disease-causing gene can take several years of intense investigation, as seen in the tracing of the cystic fibrosis gene. It has been estimated that it cost about US$30 million to trace this gene, yet if a map had existed the cost may have been only US$200,000. A more detailed map decreases the amount of DNA that must be searched through for each gene. Various leading scientists have called for an evaluation of the project priorities after the map is completed, to use the money in the best way to encourage research (Leder, 1990). This also means that the first regions of the human genome to be sequenced will be ones that are known to have disease-associated genes present. In the initial phase some of the funds for the DOE and NIH projects came from existing research funding. The NIH is spending equivalent to 2-3% of its total budget on the genome project, which in view of the importance of a coordinated mapping project, is worth the cost (Cook-Deegan, 1994).

Given the potential direct medical benefits of the project, the research money that is being spent on this project, and possibly more, can be ethically justified from the principle of beneficence. From the ethical principle of justice, other countries who can afford to pay and will benefit should share the cost of the project. The reasons for more countries to join in the project is not entirely because of their recognition of the principle of justice, but includes more the elements of potential economic benefit, and fear of being denied access to the databases.

In 1993 the US funding for the human genome project from government agencies was about US$170 million, with about US$80 million from industry. In 1992 eight genome-related companies were established, as the project became more commercial (Anderson, 1993). There are private companies embarking on the project (Kanigel, 1987). Private companies should perform such research and be able to recover costs if they are still more economical than government research, providing the results of mapping and sequencing are openly accessible. In practise much of the project will be publicly funded, but contracts to do the work may be awarded to whoever is the most competitive.

In France two private nonprofit groups (Centre d'Etude des Polymorphismes Humain and Généthon) are spending more money than the French Government on genome mapping, in pursuit of genes for humanitarian reasons, rather than economic ones. The role of nonprofit private organisations is also very important in biomedical research in other countries, leaving less room for economically motivated private companies. Time magazine (8 February, 1993) has said that the French genome project is on higher moral ground than the US project, because it is donating the results to the United Nations and is not seeking gene patents.

Data-Sharing And Patenting

The international mapping and sequencing is being coordinated by the Human Genome Organisation (HUGO). Coordination of the international effort is needed to avoid duplicity of effort. The European Commission is also coordinating research in Western Europe, and UNESCO has interests in coordination of worldwide research. Although people recognise the importance of mapping, many researchers remain more interested in pursuing specific disease-causing genes. Therefore more attention has been paid to chromosomes 21, 7, and X, which have unknown disease-causing genes.

A threat to data-sharing came following applications by the NIH for patents on cDNA sequences of several thousand genes, before their function was known. The US Patent Office rejected the first cDNA patent applications on all three grounds needed for patents: novelty, non-obviousness, and utility. They said that they could find some partial sequences in existing databases so the application lacked non-obviousness; and they also said it lacked novelty since they used a publicly available cDNA library (Roberts, 1992). Several U.S. companies have also filed patent applications on cDNA fragments (Anderson, 1993), and one Japanese company has applied for patents on 60 partial sequences of full-length cDNA clones which have had their gene function inferred (Swinbanks, 1993). Varying points of view have been expressed by patent lawyers (Adler, 1992; Eisenberg, 1992, Kiley, 1992).

There is the already existing problem of data-sharing from the viewpoint of individual competing scientists. The new technology, for example automated DNA synthesisers and the PCR, makes replication of results very rapid, which could encourage researchers to delay publication while they get more of a head start in the next stage of the research. In a system where academic jobs depend on the number of publications everyone wants to get papers published. The self-interests must be considered for the sake of the researchers' autonomy and their future work. Researchers may not reply to letters requesting data, or just reply within a selected peer group. The U.S. NIH and DOE guidelines stipulate that data and materials must be made publicly available within 6 months of generation, and earlier if possible. The guidelines are rules for those receiving grants from the NIH or DOE genome project, but encourage researchers to share information, to avoid bureaucracy. The results of discovering a disease-causing gene, or a detailed map which advances the discovery of such genes by many years must outweigh the short-term interests of individual scientists.

An example of the collaboration is between the 30 research teams working on chromosome 21 (it contains the Down's syndrome and Alzheimer genes), who produced a physical contig map (Chumakov et al., 1992). In this respect the genome map may be the ultimate collaborative research project. The most rapid progress will come from immediate data-sharing, and it is a chance for "scientific altruism" on a global scale. There is an ethical obligation on researchers, especially those using public money, to share data as soon as it is available. However, the financial size of the biotechnology industry that stems from molecular genetics is large enough to have already affected the way that data is shared. The net effect has probably been positive to this time, because of the large share of genetics research that is being performed in biotechnology and pharmaceutical companies.

Ethics and Law of Patenting DNA

There are two basic approaches to applying patent law to biotechnology inventions. In the USA, Australia, and many other countries, the normal patentibility criteria shall apply, that is, the invention has the attributes of novelty, non-obviousness, and utility, and the invention should be deposited in a recognised depository (OTA, 1989). While a country may accept the first type of criteria, some countries have specifically excluded certain types of invention. What is ethical is not the same as what is legal, though we can attempt to reduce the difference (Macer, 1991). Concerns over ethics have affected patent laws, for example European countries who joined the European Patent Convention have barred the patenting of plants or animals. Denmark has an even stronger worded exclusion in its national law. There is public rejection of the idea of patenting animals in some countries, and the patenting of human genetic material is potentially more contentious.

To qualify for a patent an invention must be novel, non-obvious and useful. If the claimed invention is the next, most logical step which is clear to workers in that field, than it cannot be inventive in the patent sense. If a protein sequence is known, than the DNA sequences that code for it will not in general be patentable, unless there is a sequence which is particularly advantageous, and there is no obvious reason to have selected this sequence from the other sequences that code for the protein (Carey and Crawley, 1990). In the case of natural products there are often difficulties because many groups may have published progressive details of a molecule or sequence, so it may have lost its novelty and nonobviousness. These are essentially short pieces of the human genome. There are also patents on protein molecules which have medical uses. In this case the protein structure is patentable if it, or the useful activity, was novel when the patent was applied for. The invention must also be commercially useful. There are patents on short oligonucleotide probes used in genetic screening. If someone can demonstrate a use for a larger piece of DNA than they can theoretically obtain a patent on it. An example of a larger patentable section of genetic material would be a series of genetic markers spread at convenient locations along a chromosome. Another set of genetic markers on the same chromosome can be separately patented if they also meet those criteria. The direct use of products, such as therapeutic proteins, is well established. The genetic information can also be used to cure a disease, for example using the technique of gene therapy with a specific gene vector.

With the completion of the genome sequence of many organisms, including humans, most genetic material will no longer be novel as it will be available in a database. The completion of the genome maps and sequences of many organisms will have many implications for the future of biotechnology patents.

Patenting has become an issue in population genetics primarily in relation to the patenting of products derived from the genetic material of indigenous peoples. In 1993, a patent filed by the United States government on the cell line of a 26 year old Guaymi Indian woman from Panama was opposed by the Guaymi General Congress, the World Council of Indigenous Peoples, the Rural Advancement Foundation International, and the World Council of Churches (RAFI Communique, Jan/Feb 1994). The patent claim was subsequently withdrawn, but on March 14, 1995, genetic material isolated from a man of the Hagahai people from Papua New Guinea's remote highlands was patented in the USA. The NIH withdraw its claim at the end of 1996, but after provoking much controversy and distrust of scientists.

These patent applications have served to cast deep suspicion on the motivation behind human population genetics research in general. Although the primary aim of most researchers is the pursuit of knowledge, and not commercial gain, and scientists with other motives may be excluded from particular projects as the HGDP maintains, nevertheless, the possibility is that products derived from genetic material collected in population genetics research could be patented for commercial purposes. Moreover, as in the case of Moore vs Regents of the University of California (1990) (Nuffield Council, 1995) where the Supreme Court of California ruled that John Moore does not have property rights in the cells taken from his body, the people who take part in population genetics research may stand to gain nothing from whatever patents that are granted on products derived from their genetic material.

The public attitudes to the patenting of human genetic material is rather negative (Macer, 1991, 1992a, 1992b, 1994). The negative reaction reflects the general feeling that genetic material is special, and should be different to other types of information. Patenting is said to reward innovation, which is a basis of the successful modern democratic and Asian economic systems. They do recognise property rights in inventions. However, there is an existing difference in the protection of property rights compared with other rights in international law and declarations of human rights. Property rights are not absolutely protected in any society because of the principle of justice, for the sake of "public interest", "social need", and "public utility", societies can confiscate property (Sieghardt, 1985). Therefore there is an existing precedent for exemption from property ownership, which is the point of the exclusiveness of patents, when some property is of great benefit to the public.

Using a more positive argument, the knowledge gained should be considered as the common property of humanity. There is an existing legal concept that things which are of international interest of such a scale should become the cultural property of all humanity. It can be argued that the genome, being common to all people, has shared ownership, is a shared asset, and therefore the maps and sequence should be open to all. All people can say that the sequence is 99% similar to their own. In the United Nations Declaration of Human Rights, Article 27 there are two basic commitments that many countries in the world have agreed to observe (in their regional versions of this declaration). These are (italics added for emphasis) (1) Everyone has the right freely to participate in the cultural life of the community, to enjoy the arts and to share in scientific advancement and its benefits. (2) Everyone has the right to the protection of the moral and material interests resulting from any scientific, literary or artistic production of which he is the author (Sieghart, 1985). An important question arising from section (2) is whether all people are the author of information that is shared by all people? The writers of this declaration may not have considered DNA, but it would certainly be in the spirit of the Declaration to interpret the DNA sequence as shared ownership. In section (1), everyone has the right to freely share in scientific advancement. This article expresses two important and relevant guiding statements of law that reflect the ethical principles of justice and beneficence, and the idea of legal property rights.

The common claims for authorship of the genome should be considered in all aspects of the genome project, especially in the questions of who should make the decisions in the project and the use of data (Macer, 1991). Some of the common factors that derive from the shared ownership are that the utilisation must be peaceful, access should be equally open to all while respecting the rights of others, and the common welfare should be promoted (Knoppers and Laberge, 1990).

The authorship of the genome can be answered in two ways. The DNA could be viewed as a random sequence of bases, and the author is the sequencer, but this is not what we would normally talk of as an author or inventor, rather the sequencers are discoverers. The sequencers of DNA are not sequencing un-owned land but rather they are sequencing un-characterised land, the name of mappers is rather suitable for this analogy. The DNA is not random, it is merely unknown. Only the method for sequencing, or mapping, can be invented and patented, and whether that side of the project can be ethically patented lies more with the question of benefit and utility as discussed above.

If these arguments are insufficient to dissuade the private ownership of genome data, in addition to the precedents for exclusion of patents, public opinion could force a policy change over the patenting of such genetic material. In the USA the commercialisation of human cells and tissues is generally permissible unless it represents a strong offence to public sensitivity. The sale of the human genome map and sequence data may be a strong offence to many and incite adverse public reaction forcing legislators to exclude it from patenting (Macer, 1991). The debate will continue, as companies will naturally desire to obtain some information protection for their investment, but they will have to be sensitive to strong public feelings that could easily be aroused, which as argued, has an ethical backdrop.

The idea that the human genome sequence should be public trust and therefore not subjected to copyright is the position of the French government, and was also the conclusion of the U.S. National Research Council (1989), and the American Society of Human Genetics (Short, 1988). The European Parliament "Human Genome Analysis" program limits contracting parties' commercial gains with the phrase "there shall be no right to exploit on an exclusive basis any property rights in respect of human DNA" (European Parliament, 1989). This idea would also include the option that the donor of genetic information, in terms of a cell line, should be able to make that information publicly available, which is usually a reasonable interpretation of the motives for patients to provide material for medical research, the motive to aid humanity in general rather than a commercial interest. The European Parliament 1993 patent rule may allow "farmer's privilege", so that farmers pay royalties on a patented gene in a seed or livestock only once, not every time the gene is passed to a descendant. It will also forbid the patenting of cloned "human parts".

Some human genes and proteins that have medical use are patented, and this type of patent has brought about huge profits for some proteins. The annual market for the protein erythropoietin in the world is over US$500 million, and some similarly profitable proteins will be found in the future. Some awards are required for promotion of the biotechnology industry and medicine. However, many people object when a routine medical technique is withheld from people who cannot afford to pay for it. Disease-related genes will be sequenced by the project, and some patents may be issued on screening methods and genes. Patent fees are being requested on the cystic fibrosis gene, even though the patent is not yet awarded. For some researchers, such patent fees may discourage studies. European researchers are challenging these royalties, and we can expect this issue to be as controversial as the cDNA patents discussed above.


There are major applications and implications of the genome project for much more than molecular and cellular genetics. It will be a huge resource of information for medicine in the next century. There will be much useful information arising prior to the completion of the project, as growing numbers of disease causing and susceptibility genes are sequenced and the mutations characterised. Most of the major single gene disorders and some of the genes involved in complex diseases should be known within the decade. It will be possible to develop DNA probes to diagnose any known genetic disorder and also will be easier to characterise new disorders.

It will expand the number of human proteins that can be made by genetically-modified organisms, which would allow conventional symptomatic therapy for many more diseases, which could be supplemented by somatic cell gene therapy when appropriate. It would also expand our basic knowledge of human biology, which allows medical treatments to be developed. We may not be able to predict when therapies will emerge after the genes are discovered, because there can still be a long delay in clinical applications following biochemical understanding. The amount of new knowledge is hard for us to comprehend, it will take decades to process it all, but it offers the potential understanding of all genetic diseases sometime during the next century.

Genetic Screening

Every person has a different genetic sequence, except for identical twins. Genetic screening involves the use of the binding between the nucleotides A-T and G-C. A sample of DNA is taken from a cell, and then the DNA is split into single chains. The bases in this single-stranded DNA will bind to the complementary bases of a nucleotide probe. The presence or absence of particular DNA sequences that represent different genes or mutations can be screened for. There are many types of genetic disease, some minor and others untreatable and fatal. One of the most common genetic diseases is inherited forms of cancer.

Prenatal genetic screening involves screening of the fetus, inside the mother's womb. There are several safe and commonly used methods to allow samples to be taken from the fetus (Macer, 1990). In addition to noninvasive ultrasound imaging, and the invasive sampling methods of amniocentesis and chorion villi sampling, new methods are being developed.

Two other techniques that are expected to have greater impact in the future, as discussed in former chapters, are isolation of fetal cells from maternal blood, and preimplantation diagnosis. Isolating fetal cells from maternal blood is advancing rapidly, and has been used for diseases such as sickle cell anemia and thalassemia (Cheung et al., 1996). If the number of false positives found in these tests, which is non-checked could mean that an unaffected fetus is aborted, is reduced and the rate of false negatives made very low, we can expect this to become mainstream and offered to all pregnant women.

Preimplantation screening on the other hand has the advantage of selection before implantation but must be associated with embryo transfer afterwards, which requires a higher level of technical commitment and cost. Enough babies have been born to confirm its initial safety, and it is certainly less traumatic than abortion after prenatal diagnosis, at the earliest at 6-8 weeks after conception. However, it might never be widely provided, as it is limited to infertility clinics, and to parents that know that they carry a disease. It might be more ethically acceptable to using abortion, so the spirit of parental autonomy would support the provision of such services even when prenatal diagnosis is available, but it is unlikely that we could ethically justify the government funding such tests unless they provide services for general in vitro fertilization and embryo transfer for infertile couples.

Prenatal genetic screening of the fetus can be used to detect characteristics of the fetus, and should only be performed for serious diseases. These include diseases that would result in serious mental or physical health damage to the fetus. In most cases the fetus is found not to be afflicted, thus removing much anxiety from the parent's mind. Without the use of such tests to confirm the absence of disease, some mothers would have an abortion. In the case that the fetus is found to be afflicted from a disease there are two different possible courses of action. If there is a therapy available and treatment before birth is necessary to avoid health damage, the fetus can be treated for the detected disease. There have been increasing numbers of operations performed on fetuses in the womb (in utero), which have avoided permanent health damage to the fetus. Sometimes the fetus is removed from the womb, operated on, and then replaced to complete normal gestation. If the detected disease is untreatable, and is serious, then the option of selective abortion is available.

There is considerable variability in the abortion laws of different countries around the world, but in general selective abortion of fetuses suffering from a genetic disease is a respected moral choice of the mother. There is clear public support for prenatal genetic screening in most countries that have been surveyed, and that it also should be available under government funding (Macer, 1994). There does need to be control over the use of cosmetic screening and therapy (that has no compelling medical reason), especially when it affects children. The human genome project raises similar ethical and legal issues to those in current genetic screening, such as confidentiality of the results. However, it will lead to screening on a huge scale, for many disease traits and susceptibility to disease (Holtzman, 1989; Muller-Hill, 1993). It is important that we deal satisfactorily with the test cases, before we are faced with all these new information. The technology may change the way we think. The amount of information obtained will overwhelm existing genetics services, and geneticists. More training of genetics (as well as ethics) will be required for health care workers, scientists, and the general public (Macer, 1990).

Will society allow individuals to have free choice over the use of genetic manipulation and screening when there is no medical reason for it? Screening can be used both to reduce individual differences to others, and to highlight differences. The arguments used against genetic intervention which has no therapeutic value include: it would be a waste of resources, may present risks to offspring, it will promote a bad family attitude, will be harmful support of society's prejudices and may reduce social variability. It will probably not have any significant affect on genetic variability as there will be plenty of alternative healthy alleles. There could also be the idea of a natural genetic autonomy, that we should let the genes come together naturally, and let the individuals develop their genetic potential without unnecessary interference by parents or society (Macer, 1990). A criteria for transgenerational ethics is that not only must a gene alteration be safe, but it must be good therapeutic sense over many generations. There must be unquestionable objectives and benefits, for many generations.

A common feature of many issues raised by the human genome project data is that we need to consider the effects of knowledge and technology on future generations. The beneficiaries and those at risk may not yet be existing. In the sense of benefits and risks, it is their genome project more than ours. We have an obligation to the future from the principle of justice (Rawls, 1971). We need to ensure future generations retain the same power over their destiny as we do, while benefiting from the culture and technology we have developed. Society's interests not only should transcend proprietary rights, but the special nature of the genome project and the claims that we can all make upon the genome should make the shared authorship and ownership legally compelling (Macer, 1991). That is why UNESCO has drafted a Declaration on Protection of the Human genome which is in Appendix 1.

Privacy and Discrimination

The information about whether an individual has a particular DNA sequence and gene, can be very powerful, especially in the diagnosis of genetic disease. It is very important that privacy is respected, because the information in a person's genes identifies some of our risk to disease that medical insurance companies and employers could use to discriminate people (Holtzman, 1989; Macer, 1990; Muller-Hill, 1993). There are already cases of discrimination of individuals after genetic testing in North America (Billings et al., 1992).

There is less experience with presymptomatic genetic testing of disease risk, such as for Huntington's disease. This is another area where the data needs to accumulate before we will be able to make reasonable predictions about the more widespread use of such testing.

DNA sequences can be used to identify individuals, and have been used for forensic cases. When the DNA is specifically cut up by restriction enzymes and the pieces are separated unique patterns are made, called DNA fingerprints. They have been used for hundreds of court cases around the world. In several countries a genetic register of criminals has been established. DNA fingerprints are also used for immigration cases to prove genetic parenthood. There have been disputes about the probability of two individual's DNA fingerprints matching, and calculations have recently been revised, but there is still a low probability of such fingerprints matching (when the size of the fragments of DNA made after digestion with the restriction enzymes, are the same in two individuals).

The question of fairness in the use of genetic information with respect to insurance, employment, criminal law, adoptions, the educational system and other areas must be addressed. In those countries with private medical insurance, some people may be put into high risk or uninsurable groups because of genetic factors (for example, high blood cholesterol, or family history of diseases). Some insurance companies and employers perform screening in the USA (OTA, 1990). Some legislation has been passed in the USA, such as the Americans with Disabilities Act in 1990, or the proposed Human Genome Privacy Act. However, there is only one solution, that is a national health insurance system with equal access to all and no discrimination based on disease risk factors that people have no choice over.

Gene Therapy

Many genetic diseases may be able to be treated by correcting the defective genes, by gene therapy. Gene therapy is a therapeutic technique in which a functioning gene is inserted into the somatic cells of a patient to correct an inborn genetic error or to provide a new function to the cell. There are a number of human gene therapy trials currently underway, for several different diseases including several cancers. There have been over a hundred human gene transfer or therapy trials on nearly a thousand patients approved in numerous countries. It is still an experimental therapy, but if it is safe and effective, it may prove to be a better approach to therapy than many current therapies, because gene therapy cures the cause of the disease rather than merely treating the symptoms of a disease. Also, many diseases are still incurable by other means.

Currently such gene therapy is not inheritable, we need to have much wider discussion about the ethics and social impact before we start inheritable gene therapy (Macer, 1990). However, non inheritable gene therapy to treat patients involves similar issues to any other therapy, and if it is safer and more effective, it should be available to patient's who consent to it. There are many approaches being developed and we can expect rapid introduction of these techniques, because of more than 20 years of preparatory experiments on animals, and the success of some of the current clinical trials.

We can distinguish gene therapy from genetic engineering for ethical debate, by the therapeutic motive. It is better to leave the term human genetic engineering for genetic intervention which is not aimed at direct therapy. However, we may still think of cases where indirect medical benefit can be given, such as improvement of the efficiency of the immune system by genetic means or genetic vaccination. Cosmetic uses of medicine are commonly available from the private medical sector, and it may be difficult to limit the cosmetic use of gene therapy in the future when cheap vectors and delivery systems have been developed. Public opinion supports the use of gene therapy for treating disease, in India as in other countries (Macer et al. 1995).

Population Genetics

Population genetics is a discipline studying genetic variation in defined populations, including relevant aspects of population structure and geographic variability of DNA sequences and their frequencies. Their changes in time and space are controlled by evolutionary factors, including mutation, natural selection (i.e. differential mortality and fertility of genetic types), drift (stochastic fluctuation tied to the demographic size of populations) and migration. Population genetics deals with the characteristics of genes within a population as opposed to the description of the genes in a particular individual (Chee et al. 1995).

The biological relationships of human population groups is of broad interest to the understanding of human history. Classical studies of genetic diversity have been dealing with antigen, protein and enzyme polymorphisms, for example HLA or blood groups. Modern genetic studies are based on the molecular analysis of DNA polymorphism. Classical studies look at expressed sequences, which represent less than 10% of the genome, whereas molecular genome diversity studies are mainly concentrated in parts of the genome that are often not expressed at the phenotypic level.

Isolated populations are the main source for observation of genetic forces acting in human evolution. While gene frequency across different populations varies for specific diseases; the total effect of genes on mortality appears similar. Comparative studies can be made on the differences in the mortality and fertility as well as on anthropometric data between consanguineous and non-consanguineous groups. They can be used to test genetic susceptibility using polymorphic markers in different communities, which can also examine genetic susceptibility to environmental agents. This makes possible the prevention of certain multifactorial diseases by careful avoidance of exposure to environmental agents.

Consanguinity and large family size are very interesting for population genetic studies, but studies of consanguineous marriages of families have the potential to raise numerous ethical and social issues. There are opportunities for genetic epidemiological research in countries where consanguineous marriage is a long-standing tradition. Such research projects can use data from many sources, for example, birth and death records, family register books, or anthropological or medical surveys, and socio-economic data in order to test inbreeding effects (Chee et al. 1995).

The first genetic studies in populations came from surveys all over the world looking at frequencies of single gene diseases. Others were conducted on sampled individuals from target populations. Based on these studies, mass screening programs for particular disease genes were adopted e.g. in Cyprus for thalassemia, or in many countries for PKU in newborns. Genetic screening and genetic testing have been discussed by numerous persons and organisations over the last twenty years (recent reviews include: Macer, 1990; Chadwick et al., 1993; Murray, 1993; McCarrick, 1993; Nuffield Council, 1993; Nielson & Nespor, 1994). Many of the issues in current genetic screening programmes are relevant to population genetics research, but some significant issue are different, such as the notion of group consent. Moreover, while at present we are focusing on research we should also foresee the applications and benefits flowing from the human genome project that could well apply to whole populations. Therefore the ethical considerations must be carefully treated, since whole groups of asymptomatic individuals are the targets rather than single individuals who come forward themselves.

More recently, molecular biology has enabled geneticists to work out the spatial and temporal variation of gene frequencies. Several projects have started independently in different countries others, such as the human genome diversity project (HGDP), proceed as an international addition to the human genome project (HGP).

Human Genome Diversity Project

One example of population genetics research is the Human Genome Diversity Project (HGDP) described by L. Cavalli-Sforza as "an international anthropology project that seeks to study the genetic richness of the entire human species". The name comes from a proposal in 1991 in the journal Genomics to make a systematic study of the genetic diversity of human populations. However, like the Human Genome Project, it shares a much older origin in the work of population geneticists over many decades (Cavalli-Sforza et al., 1992; 1994; Cavalli-Sforza & Cavalli-Sforza, 1995). The Human Genome Organisation (HUGO) responded to the 1991 proposal in the journal Genomics by establishing an ad hoc committee to develop the global project. The HGDP is being developed under the auspices of HUGO to promote global involvement and coordination.

The scientific aims of the HGDP stated in the 1994 HUGO Summary Document are:

a) "to investigate the variation occurring in the human genome by studying samples collected from populations that are representative of all of the world's peoples,"

b) "and ultimately, to create a resource for the benefit of all humanity and for the scientific community world-wide. The resource will exist as a collection of biological samples that represents the genetic variation in human populations world-wide and also as an open, long-term, genetic and statistical database on variation in the human species that will accumulate as the biological samples are studied by scientists from around the world."

The main scientific value of the HGDP is:

a) deepening our understanding of human history and identity.

b) gaining knowledge about the environmental and genetic factors involved in predisposition and resistance to disease, so-called genetic epidemiology.

c) encourage the development of local laboratories where the collection of genetic samples will be collected and analysed.

Even though to date there have been numerous studies on the development of culture, language and population genetics and some consistency between genetic, cultural and linguistic observations has been found, a survey of more populations in a more systematic way will extend what we already know and test current theories. Linguistic differences suggest there are about 5,000 population groups in the world. In the short term the HGDP will attempt to study about 500 of these populations. Even if some populations refuse to enter the project, there are still many other populations that could be surveyed. It is expected, then, that the project will be able to obtain samples from a large number of willing populations. If funding does not permit such wide sampling there is still scientific merit in collecting data from a smaller number of populations.

The HGDP initially planned to centralise the collection of samples from isolated populations, some of which are already under investigation in population genetics research. This led to fears among some members of indigenous groups that the knowledge could be used for further ostracisation (Lock, 1994). However, the HGDP is now moving away from both the idea of central control to regional control and from the focus on indigenous populations, to include all populations. Personal anonymity would be maintained by not having the names of individuals in the central repository, and by observance of established privacy rules.

The establishment of cell lines allows maintenance of a permanent record of the DNA of individuals of a population. At least two independent and physically separate collections in different countries should be kept, to maintain the resource. The HUGO HGDP committee has said that access will be free, with some compensation for maintenance costs. Any data would be shared back into the main database, which would also include computer databases of genetic map and sequence data. There are also efforts to develop less expensive storage and microsatellite marker techniques that can be used in local laboratories that have limited resources, to ensure their fuller participation.

Ethical issues of population genetics research

Given the transnational nature of population genetics studies, the issues raised were the subject of a study by the UNESCO International Bioethics Committee (Chee et al. 1995). The report has been available on the Internet since completion in November 1995. Key points of the UNESCO report were (Macer et al., 1996):

1. no endorsement of a particular population genetic project;

2. call for establishment of a separate ethical committee that is available to all population genetics researchers;

3. discussion of variety of ethical, ethnic and social issues.

The ethics of population genetics should be formulated with reference to the minimal agreed human values as expressed in international human rights law. Central to our human rights obligations is the promotion of "respect for, and observance of, human rights and fundamental freedom for all without distinction as to race, sex, language, or religion." (Charter of the United Nations, Article 55 (c). The Universal Declaration of Human Rights is founded upon the notion that there are universally recognised human values and that these values are inherent in the human individual (Chee et al. 1995).

The importance of obtaining consent from a study population is well recognised (even if not always practiced). Population genetics studies should be conducted by personnel with the appropriate qualifications, but only after informed consent has been given for any general medical examinations, and removal of blood samples or other bodily samples. The doctrine of informed consent is applied to both medical treatment and research. Before a person is asked to consent to any sampling or treatment they must be provided with certain information. This information includes (in language the patient can understand) a description of the procedure - which is generally easy, and should be risk free if accepted medical procedures are used for sampling, and a description of the risks and benefits of the resultant information.

Even when correct information is carefully presented in culturally appropriate ways, it cannot be guaranteed that it has been understood. The ethical obligations that are achievable include accurate delivery of information together with the disclosure of relevant risks and benefits to the individuals and communities involved, in language that is accessible to the potential research subjects, considering cultural and religious needs and aspirations of particular communities. There is an obligation or duty on the part of scientists to properly inform potential participants.

It is important to identify the most appropriate persons with whom to communicate, the persons from whom clearance should be obtained, and the appropriate content and media of communication. If the research methods involve the use of saliva, skin, hair, or blood samples it is necessary to ensure that the collection of these body samples does not violate cultural norms and concepts relating to the human body and its functions (Chee et al. 1995). Of course the most difficult group consent question is who can give group consent for the genome project itself - a question that no one has been able to answer (Macer, 1991).

As discussed in following papers, various groups of indigenous peoples have expressed their irritation with past population genetics research which they claim has been conducted without prior consultation and in a way where consent was obtained in terms inconsistent with their cultural norms. Practitioners of contemporary science do not always understand that the goals and aspirations of scientific projects may not always coincide with the goals and aspirations of particular cultures. It may not be ethically acceptable to some people to cooperate in the collection of saliva, skin, hair and blood samples for the purpose of storage and the establishment of "transformed cell lines", samples which would be basically identical to the individual of origin which are then made available for study to scientists around the world. Therefore many representatives of indigenous peoples have expressed strong concerns about the HGDP.

The planners of the HGDP got off to a bad start with misunderstandings and fears widely expressed among indigenous peoples. Because the HGDP was planning to collect blood samples some groups called the HGDP the "Vampire project" (Lock, 1994), while other groups were angry because they believed that they were possible target populations even though no community representatives had been contacted about the Project. The Mataatua Declaration on Cultural and Intellectual Property Rights of Indigenous Peoples of June 1993 is a call for a halt to the HGDP until its impact has been discussed. Article 3.5. of the Declaration calls "for an immediate halt to the on-going 'Human Genome Diversity Project' (HUGO) until its moral, ethical, socio-economic, physical and political implications have been thoroughly discussed, understood and approved by indigenous peoples". The Declaration is actually not anti-science, and includes a call for involvement in scientific research, recommendation 2.11, "Ensure current scientific environmental research is strengthened by increasing the knowledge of indigenous communities and of customary environmental knowledge".

In fact the HGDP included all populations, not only indigenous populations. Since that time, the HGDP goals have shifted somewhat, but there has been a series of Declarations directed against this project (Mead, 1995). The HUGO HGD Summary Document includes ethical guidelines which do address the question of participation, consent, and commercialisation (HGD, 1994); as does the HUGO Code of Ethics (in the Appendix). The Human Genome Organization (HUGO) Ethics Committee Code of Ethics for genetic sampling stresses similar issues to those raised by the UNESCO subcommittee. It starts from the same principles: Recognition that the human genome is part of the common heritage of humanity; Adherence to international norms of human rights; Respect for the values, traditions, culture, and integrity of participants; and acceptance and upholding of human dignity and freedom. The HUGO - ELSI Committee Code of Ethics was endorsed by HUGO in March 1996. It recommends principles for genetics research based on: scientific competence, understandable communication (two way), consultation with participants, free and informed consent, respect the choices of those involved, confidentiality, international collaboration, avoid conflict of interest, undue inducement through compensation, and continual review of the research.

Nevertheless, the controversy continues. In February, 1995, a forum of Indigenous Peoples in Asia issued a statement to the European Parliament in which they strongly opposed the HGDP and called for it to be stopped (ARCW, 1995). The Beijing Declaration of Indigenous Women formulated at the United Nations Fourth World Conference on Women (30 August - 8 September 1995) demanded "that the Human Genetic Diversity Project be condemned and stopped" and that their "intellectual community rights" be recognised.

There are numerous other ethical issues which are common to the HGP and the HGDP. Many issues relate to individual privacy and possible abuse of genetic data by insurance companies and employers. DNA collected from population groups would present analogous problems relating to the adequate protection of privacy (Annas, 1993); but the meaning of privacy could vary across cultures. Furthermore, it is important to note that in population genetics research confidentiality issues have to be considered at the community level as well as at the individual level.

One way of ensuring confidentiality for individuals would be not to collect or keep identifying information in the central repository. This would, however, limit the scope of research that could be done. Confidentiality for individuals in human population genetic research may be protected to a certain extent through coding and anonymity, with strong safeguards to protect the identifying information that is kept in the central repository. If all members of a community, or a population group, were found to have a gene that predisposes them to a common late onset disease, for example, could that information be protected? Health insurance companies could cancel or refuse health insurance to a population, in the same way that health insurance has been denied to individuals or members of a family in countries that do not prohibit genetic discrimination by law. In several countries, these cases have led to legislation on genetic privacy. Although the principle of confidentiality is included in the Outline of the UNESCO Declaration on the Protection of the Human Genome (see Appendix 1), further national efforts to protect against such abuses may be required.

Patenting was discussed in a separate section above. While there could also be provision for a one-time gift of cells or blood with no conditions, as is found in some tissue donation forms for blood and body tissues, can one individual sign away commercial rewards to future research knowledge for the population to which they belong? Financial returns are not the only form of benefits of research results which could be returned to subjects of research. At the individual level, the results of physical examinations and clinical diagnosis and options for treatment are sometimes communicated to each participant in the local languages through local health authorities and doctors. The provision of health and medical care should be appropriate to the cultural and social context of the community and should be sustained. In this, the principles of primary health care as contained in the Alma-Ata Declaration (WHO/UNICEF) of 1978 should serve as a good set of guidelines to follow.

At the community level, the health data could be utilised for the improvement of local community health. Thus, benefits should also flow back to the groups and communities in the form of contributing to the formulation and implementation of local and national health care policies that would enable communities to better their positions. These policies, as well as the health care services which are offered, should of course be decided upon by the communities.

Some challenging implications may arise from the better understanding of human history that population genetics research could provide. The new knowledge from such research could be used to educate people of indigenous groups that would help protect their interests. On the other hand, new knowledge of human group evolution and the relationships of particular groups to others, may challenge existing world-views. Some population groups have strong beliefs in mythologies or cosmogonies which explain group origins and identity, and the return of data that challenges the accepted beliefs could be a delicate issue.

One fear that has been expressed about population genetics research is that access to and knowledge of a community's complete genetic make-up makes it theoretically possible to devise cheap and targeted biological weapons trained solely on that community (RAFI Communique, 1993b). Given that greater genetic diversity exists within any particular population group than among population groups, it is highly unlikely that specific genetically-based genocidal weapons could be developed for specific population groups.

Public attitudes towards population genetics are often based on social ideologies, racism, and eugenics and can well lead to stigmatisation and genetic reductionism. Population studies in the past have shown that most of the genetic diversity is to be found within every race or population, and if this is further confirmed to be true the typological classification of humans into different "races" is scientifically invalid. Nevertheless "racism" as an ideology and as an attitude is a human reality.

Eugenics is a word coined by Francis Galton in 1883 meaning good genes (Macer 1990). He refered to the "science" of improving human stock by giving "the more suitable races or strains of blood a better chance of prevailing speedily over the less suitable". A danger is that genetic findings may be understood as the only story of human, biological, and cultural evolution. People believe genetic explanations of human behaviour, as can be seen in the scientific and popular press over the past decade (Nelkin & Lindee, 1995).

Stigmatisation may occur when population groups in which there is a high incidence of genetic disease are selected for scientific investigation thereby drawing attention to their genetic differences. Care needs to be taken that targeted groups do not become stigmatised in some way simply because they are of scientific curiosity, or because they are more frequently studied and more is known about them they seem to have a greater predisposition to disease. Such stigmatisation can lead to unjust discrimination.

"Genetic reductionism" means judging individuals with reference only to their genetic inheritance. Western science has frequently sought to explain the whole by a greater knowledge, by a part that is deemed to be most fundamental. Genetic reductionism is a misunderstanding of science and also represents a threat to those mythologies or cosmogenies which are different from the dominant world cultures.

One of the fundamental points of opposition of indigenous groups towards genetic studies of human history is that the results may contradict indigenous people's views of oral and traditional history, and the meaning of genes and genealogy. For example, Maori people have two words to describe the human gene, one meaning "life spirit of mortals (Iratangata)and the other genealogy (Whakapapa), which connects Maori with themselves and others (Mead, 1995). The gene and genome are not the property of individuals but rather are part of the heritage of families, communities, tribes and entire indigenous nations. In this regard the UNESCO position on the human genome being part of the common human heritage is more compatible with the views of indigenous persons, than the view discussed in the patent section of those seeking patents on genes.


Population genetics research involves contact with and sampling of different populations. This presents opportunities to involve researchers and participants in a two way process of education. The researchers should involve local participants in the research. This presents a chance for advanced genetics training, and training in taking consent and consultation from participating groups of people. The process of anthropological research actually involves education of the researchers in the local customs and beliefs, which can then be shared with the rest of the world in efforts to help understanding among peoples.

The people participating in the research will be able to learn of the reasons why the sampling is sought and of the research goals. They may be interested to meet people from out of their community, though the contact should not create expectations which cannot be fulfilled. There is the need to share results. Some representatives of indigenous populations, however, have expressed concern that they do not want to know the results of scientific studies that challenge their local understanding of history. There is also the education of researchers during the process of their search negotiations and of the results of any investigations, of the attitudes of local groups and populations. The process of anthropological research actually involves education of the researchers of the local customs and beliefs, which can then be shared with the rest of the world in efforts to help understanding among peoples.

If education of genetics, as well as the bioethical issues it raises, is increased, many hope this would reduce the tendency for racism. Advances in biology and medicine have generally led to pressure upon educators of how students can be prepared to face the ethical dilemmas that the technology often raises. In school and university education during the 1960s to 1990s in many countries science has been taught independent of social or ethical values. However, science educators have discovered during the last two decades that the most efficient way to educate science is to discuss the science together with examples of technology and put the facts into the social context. This method of teaching is generally called the Science, Technology, and Society (STS) approach (Ramsey, 1993). Bioethics is one part of the approach of STS. There are a diversity of views on how to effect efficient education of social issues and even the science itself (Waks & Barchi, 1992), however, the point is that students learn more science when it is combined with practical applications. The problem is that value education has also been abused in the past to promote discrimination, and the weight of the word "scientific" can make people believe that such a value is also scientific. There is a need to work on what can be taught, and to promote decision-making, and recognition of human diversity.


International research projects raise the issue of how universal bioethics are, and whether different standards can be applied to different population groups and peoples. Results of an International Bioethics Survey conducted in more than a dozen countries since 1993 suggest the same diversity of opinions on issues raised by genetics is found inside each society (Macer, 1994).

There are two ways to think of the term "bioethics" (Macer, 1995), one is as descriptive bioethics - the way people view life and their moral interactions and responsibilities with living organisms in life. The other is prescriptive bioethics - to tell others what is good or bad, what principles are most important; or to say something/someone has rights and therefore others have duties to them. Both these concepts have much older roots, which we can trace in religions and cultural patterns that may share some universal ideals. If this descriptive bioethics study is correct, then the work of prescriptive bioethics in providing universal guidelines can proceed with more confidence.

While all admit the function of the United Nations system is to protect the Universal Human Rights of all persons, another function of international organizations may be to foster studies into how to best protect the interests of different groups, which can best be done after finding out what their interests are. We need to ask whether, if in the same way that our genetic diversity suggests the word "race" is inappropriate, our ethical and cultural diversity also does? The data suggests the answer is yes although our prejudices may deny this.

It is ethically and scientifically desirable to have regulatory oversight of research involving sampling of human populations, meaning a certain degree of scientific and ethical review prior to acceptance of a research protocol, once accepted, ongoing monitoring and surveillance usually are not assured. Can there be sanctions? Disciplinary measures including for example, suspension, withdrawal of privilege and fines, constitute the usual avenue of professional measures. In addition, where research subjects have been harmed, civil and criminal sanctions are also possible. Funding bodies may withdraw funds and sometimes even retroactively. If researchers are to become more accountable and actual practices more transparent, other forms of sanctions or at least of publicity, should be envisaged. Stricter, standardized reporting requirements, on a regular basis and publication of such reports are one such avenue.

If researchers are to be subject to greater scrutiny, the same holds true for the media whose duty of honest, scientific reporting and preservation of privacy needs to be underscored. Whole populations, communities and the researchers themselves have often been wrongly depicted and wrongly represented with the resulting unjust labeling and discrimination. Such practices only serve to undermine public confidence and participation in research.

Population genetics is not simply a multiplication of the individual ethical and legal issues already raised by genetic research. There are different concerns and traditions in each group under study, and even among individuals within any group. The degree of information, consultation and cooperation must reflect such differences in participants. Likewise, the role and responsibilities of the researchers and of the local and national authorities, as well as the societal implications, will differ. For the future we need consultation with populations; individual and group consent mechanisms; ongoing ethical review; inclusion of representatives of populations in decision-making; communication, education, benefits, and feedback strategies at the population level; confidential data and sample banking; continual scientific review and monitoring; and appropriate sanctions. We also need to start gathering systematically the examples of use and abuse of DNA and cell sampling, to give us the necessary knowledge to better predict the future. Above all we need to have anthropologists and scientists who seek ethical sampling.

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Appendix 1: Revised Preliminary Draft of A Universal Declaration On The Human Genome And Human Rights (UNESCO)
Appendix 2: Statement On The Principled Conduct of Genetics Research (HUGO Code of Ethics)
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