Journal ofMedical Ethics 1999;25:204-208

Indigenous peoples and the morality of theHuman Genome Diversity ProjectMichael Dodson and Robert Williamson University ofNew South Wales, Sydney and The Murdoch Institute,Royal Children's Hospital, Melbourne, Australia

AbstractIn addition to the aim of mapping and sequencingone human's genome, the Human Genome Projectalso intends to characterise the genetic diversity of theworld's peoples. The Human Genome DiversityProject raises political, economic and ethical issues.These intersect clearly when the genomes under studyare those of indigenous peoples who are alreadysubject to serious economic, legal andlor socialdisadvantage and discrimination. The fact that someindividuals associated with the project have madedismissive comments about indigenous peoples hasconfused rather than illuminated the deeper issuesinvolved, as well as causing much antagonism amongindigenous peoples. There are more serious ethicalissues raised by the project for all geneticists, includingthose who are sympathetic to the problems ofindigenous peoples. With particular attention to thehistory and attitudes ofAustralian indigenouspeoples, we argue that the Human Genome DiversityProject can only proceed if those who further itsobjectives simultaneously:*respect the cultural beliefs of indigenous peoples;*publicly support the efforts of indigenous peoples toachieve respect and equality;* express respect by a rigorous understanding of themeaning of equitable negotiation of consent, and*ensure that both immediate and long term economicbenefits from the research flow back to the groupstaking part.(7ournal of Medical Ethics 1999;25:204-208)Keywords: Indigenous peoples; Aboriginal; Human Ge-nome Project; cultural beliefs; consent; HGDP

The Human Genome ProjectThe Human Genome Project (HGP) is fundedjointly by the Department of Energy and theNational Institutes of Health in the United States,by many other government agencies worldwide,and by private biotechnology companies. Itsobjectives (in order) are to map the humangenome, to determine the sequences of the 2-3%of the genome which codes for proteins, and thento determine the entire human DNA sequence(three billion base pairs per haploid [sperm or

egg] genome). It is likely that these objectives willbe realised by the year 2001.1

Although the HGP has a monumental vision ofits own, it should be noted that many of its com-ponent parts, particularly those related to specificdiseases such as cancer and cystic fibrosis, werealready well funded prior to the establishment ofthe HGP. These preexisting targeted researchprogrammes were integrated into the HGP at itsinception, and for some years provided the basisfor most scientific advances. However, a variety ofrandom ordering and sequencing strategies (suchas those which used a set of large families to maprandom sequences, or sequenced all coding genes(ESTs), or randomly sequenced the ends ofhuman DNA fragments cloned in bacterial artifi-cial chromosomes (BACs)) proved to be lesselegant but more effective.The diseases that affect most people are not due

to inherited mutations in single genes, but involvethe interactions of several gene variants with eachother and with environment. This is the case forcancer, heart disease, Alzheimer's disease,diabetes, and even susceptibility to infection. It isalso true for behavioural traits (such as aggressionand alcoholism) and psychiatric illness. Thesediseases are very important to all communities,and also very attractive as targets both toestablished pharmaceutical companies and to newbiotechnology companies. Even if one does notaccept a facile reductionist approach to multifac-torial diseases, a genetic approach often yieldsclues as to which pathway is involved, which inturn suggests pharmacological interventionswhich could be extremely profitable.

The Human Genome Diversity ProjectWhen the Human Genome Project started, thequestion "whose genome should be sequenced"was asked many times. While all human genomeshave overwhelming similarities (particularly in theorder in which the genes occur), there are manydifferences in sequence, approximately five mil-lion between any two individual haploid genomes.Because these differences are responsible for pre-

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disposition to some diseases as well as normalvariation, and can be used for anthropological andgenealogical research, there was immediate inter-est in extending the genome project to collect andto sequence DNA samples from many differenthuman groups.23

Indigenous peoples were identified as amongthe groups to be especially targeted for genomestudies.4 ' Some of the early proposals includedcomments from the protagonists which could bedescribed politely as naive in the extreme.Indigenous peoples felt they were being treated asexamples of human fossils, from whom sampleshad to be collected before they died out. Remarkssuch as this, which were widely quoted, led to thecharacterisation of the Human Genome DiversityProject (HGDP) as the "vampire project" and arestill greatly resented by indigenous peoples.6However, for the purposes of this article we wishto put these remarks to one side, as theiroffensiveness distracts from a sensible analysis ofthe underlying issues that are involved for all sci-entists and all indigenous peoples.

Indigenous peoples do not suffer from the samediseases in the same ratios as do North Europe-ans. This is partly a result of poverty, but it also isdue to genetic differences which cause interac-tions with environment leading to health out-comes. These are not always bad outcomes - forinstance, although the incidence of heart disease,hypertension and diabetes is high amongstAustralian Aboriginal peoples, the incidence ofsome types of cancer is relatively low.One of the main objectives of studies of the

genomes of indigenous peoples is to determinegene sequences that may confer these "positive"and "negative" differences. In this way, it is hopedthat greater understanding ofunderlying causes ofpathology will lead to new methods for treatment.Pharmaceutical and biotechnology companieswish to ensure that any discoveries are patented toprotect their investment.

However, there are several practical problems,apart from the ethical ones dealt with in thefollowing sections. It was once thought that therewere many unique DNA differences between dif-ferent racial or ethnic groups. For several reasons,this is not true. First, most groups (of any kind)overestimate their genetic "purity"; there isusually more genetic intermixture between groupsthan is appreciated culturally. (For instance, inCyprus the Greek and Turkish communities thinkof themselves as very separate, but share almost allallelic variants of every gene that has beenstudied.) Second, there are few differencesbetween ethnic or racial groups which can identifya community unambiguously; sophisticated hap-

lotype constructs have to be studied to reveal suchdifferences. Finally, there are problems in definingphenotype if the relationship between genotypeand environment is confused - although thereappears to be a very high incidence of alcoholismamong Aboriginal men, it was only after colonisa-tion of Australia that alcohol became widely avail-able, and there was no alcoholism in traditionalAboriginal society.

The history of indigenous peoples, theircultures and their interactions withcolonising peoplesThere are hundreds, perhaps thousands, of differ-ent indigenous peoples, and it would be foolish toattempt to overstate the generalisations that canbe made amongst them. However, a few pointscan be made which are useful in this-context.

1. For whatever reason (whether cultural or eco-nomic), most indigenous peoples did notdevelop a society where goods were seen asprimarily the property of individuals, to bebought and sold without reference to the groupas a whole. Land and other property are oftenseen as belonging to the group (nation, ortribe, or extended family), and either cannot bebought and sold at all, or can only be sold if theentire group agrees to this after discussion.This extends to "genetic property" such asDNA.

2. Culture is seen in a more historical way than inmany Western countries, extending backwardsand forwards in time infinitely. Maintenance oftraditions may be of much greater importancethan present events, and the extended familymay be of greater importance than the nuclearfamily.

3. Culture is far more likely to be regarded as agroup or tribal property, rather than belongingto an individual, and the individual will nothave the right to offer cultural or human valuesor samples from the group any more than otherproperty, such as land. This may well apply toblood or tissue, which is usually treated withcultural respect as part of the inheritance of thegroup.

In many indigenous cultures, an individual will nothave the right to give or sell a blood sample for genetesting to a researcher without the consent of thegroup (and perhaps not at all). It would be regardedas an invalid contract with profound ethicalimplications (perhaps comparable in "Western" lawto the prohibitions on a father selling his six-year-old daughter as a child prostitute, something we

206 Indigenous peoples and the morality of the Human Genome Diversity Project

would regard as ethically outrageous in anautonomy-centred individualist society.)These cultural beliefs are deeply held and not

dependent on a history of deprivation anddiscrimination. Superimposed upon these beliefsis the fact that most indigenous peoples are livingin poverty compared to those who colonised theircountries. This poverty is associated with a loss ofland that was previously the property of the indig-enous group. The peoples were often dispossessedof land by colonisers who used many tricks, butwho also argued that this was "for the commongood". When examining the objective hardshipsexperienced by indigenous peoples, health is oftenone of the areas where they are most deprived.

In Australia, the life expectancy of Aboriginalmen is about 50 years, approximately 30 years lessthan non-Aboriginal men. Tens of thousands ofyoung Aboriginal children were taken from theirfamilies without consent (the "Stolen Genera-tion"), told they were orphans or abandoned, andgiven to non-Aboriginal families to raise. In someAboriginal communities hookworm, which is vir-tually unknown among white children and is easyto treat, is endemic. Unemployment among Abo-riginals is 41%, and is set to rise to 53% by 2006.Australia is a "first world" country, has beenwealthy for many years, has a powerful legal andparliamentary system, and a free press. In spite ofthis, the health and economic standards of itsAboriginal peoples can only be described asappalling. These statistics are reproducible to agreater or lesser extent in most countries, and areonly more striking in Australia because Aboriginalpeoples share a country with the non-Aboriginalpopulation.

Attitudes of indigenous peoples to theHGDPThe Human Genome Diversity Project raises keyquestions, such as:

* who makes decisions with regard to medicalresearch?

* who controls and plans medical research?* who benefits from medical research?* is it possible to offer "group rights" or "group

approval"?

The HGDP targets indigenous peoples who havehad little or no contact with other groups and whohave not mixed their genes with others. The focusof the project to date has been in South America,but Northern Territory (Australia) Aboriginalgroups have been approached for inclusion in thestudy.

The collected blood and tissue samples will beplaced in a biological DNA bank which will beused for research into disease susceptibility.Scientists hope that differences in susceptibilitybetween populations can be used to find genes, orgenetically determined biochemical pathways,which will give products for treating common dis-eases. This has already been proven true for obes-ity. The project is largely funded by governmentsand pharmaceutical companies. In exchange fortechnology and resources they are given access tothe genetic raw material collected by researchersfrom Aboriginal groups; the HGDP functions asan international marketplace for DNA samples.

History teaches us that the pure fascination ofscience cannot be quarantined from its broadersocial implications. The project has the potentialto exploit the genomes of indigenous peoples as aresource for multinational investment. This is notonly a denial of the rights of peoples toself-determination, but also an affront to humanethics and to the dignity of all.Examples have been quoted of blood samples

having been taken on the pretext that these werefor pathology tests of immediate clinical value, butthe samples then being used to provide DNAsamples for the HGDP. Neither the immortalisa-tion of the blood cells (which is an affront to thecultural values of many indigenous peoples) northe commercial potential of the samples is madeclear to those from whom the blood is taken. Thescientists involved in some projects claimed thatinformed consent was not obtained because thetribal peoples involved would not understandDNA research, so there was no use providingexplanations, although they then claimed thatconsent was obtained "in as much as they could".Suppose such standards were applied in other

situations in Australia, or other first worldcountries. Would working-class people be abusedlike this, and be informed "in as much as theycould"? Would this standard be applied to those ofIrish, or Italian, or Jewish ethnicity in Australia, oris the standard for indigenous peoples clearlylower than for others? Are the Arhuacos, Assarionand Guayami peoples treated differently becauseof their ethnicity, and afforded fewer rightsbecause of these differences? Is it all right to taketheir blood with only a condescending commentand no informed consent, when laws preventblood sampling from suspects of the most seriouscrimes, from the mentally ill or from children?Does anyone seriously believe that white people infirst world countries could be treated like this?

In a recent article Juengst states that it is notpossible to offer any protection to autonomousgroups by obtaining approval from them prior to

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genetic studies, and that even requesting suchapproval risks encouraging the discriminatoryattitudes which it seeks to oppose.7 Juengst alsoclaims that there are enough people from any eth-nic group who have migrated so that at least a fewwould be willing to give DNA samples (either vol-untarily or for payment) without worrying aboutthe attitudes of the group as a whole.While Juengst might be correct, at least in part,

he ignores the fact that an indigenous people isnot merely a group in the population geneticssense, but also a group in that its members arevictims of institutionalised discrimination. It isdiscrimination against an ethnic group which iscentral to the ethical issue. Although individualCatholics, for example, may be discriminatedagainst in the United States, it would be absurd tocompare their situation with that of the NativeAmerican peoples or the Australian Aborigines,and therefore the same ethical issues of groupconsent do not apply. While Juengst may stateaccurately that it is possible to circumvent amechanism for appropriate and equal dealing andconsultation, it would be unethical to do so. Thearticle following that of Jeungst in the AmericanJournal of Human Genetics reports use of a modelagreement for genetic research with a NativeAmerican tribe which shows the value of such anapproach.8As presently structured, many interactions of

genome scientists with indigenous peoples seethem as a means to an end. Researchers takeblood and go back into their laboratories, remain-ing immune to the reality of the human sufferingexperienced on a daily basis by indigenouspeoples. Researchers may come face to face withpoverty and deprivation when they collect sam-ples, and can recount these stories at dinnerparties, but remain untouched in real terms,because they are inactive at correcting these injus-tices. Because they do little or nothing to facilitatechange, they contribute to the continuation of theshameful status quo. (There are exceptions to thisgeneralisation-for instance, the research teamwhich collected Huntington's disease DNA sam-ples from Venezuela has taken an active responsi-bility for improving health care for the affectedpopulation, as has Dr Sheila van Holst-Pelikaan inWestern New South Wales but they are few andfar between.)

It is perhaps ironic that it has been estimatedthat it costs approximately US$2,300 to collecteach blood sample for the Human GenomeDiversity Project. This is more than the per capitaGross Domestic Product (GDP) of most of theworld. Perhaps at least some of this money couldbe spent attempting to ensure that indigenous

peoples are not seen only as "isolates of historicinterest", and to support their attempts to survivein their integrity.

Is there a way forward?We need to work out an ethical and realistic way tonegotiate issues such as control over researchownership. It is clearly not reasonable to insist thatindigenous peoples are the sole beneficiaries of thebenefits that flow from research; were this the casemuch research would never get done. However,benchmarks must be set out clearly. The rights ofindigenous peoples over their resources (includingtheir genetic resources) must be recognised,protected and respected.

It seems to us that the first fundamental ethicalimperative is that those who wish to obtainbiological samples from any ethnic group mustbegin by making an effort to understand theirsituation and culture and by respecting their con-cept of autonomy and their belief system. In thecase of most indigenous peoples, this meansaccepting that there may be a strong sense ofcommon ownership and cultural identity whichdoes not allow an individual to part withsomething such as DNA, whether for money orother reasons, without group consent. Scientistshave to negotiate such issues with equality andrespect, and accept answers that they may not like.If the result of such negotiations is that researchdoes not proceed, so be it; this often happens inother contexts when a human ethics committeeblocks a clinical trial on patients. It may be arguedthat research will not progress as quickly as it oth-erwise might, but this is often the outcome ofaccepting ethical constraints in medical contexts.

If a situation of oppression exists which affects agroup, it is imperative in terms of justice that wecondemn such a situation and work towards itsamelioration and elimination. Naturally, indig-enous peoples know, as we all do, that there aremany situations of injustice and oppression in theworld, and no one has the personal energy orfinancial resources to deal with them all, nor canany individual be expected to. If scientists askindigenous peoples who are in such a situation fortheir support in research, they have an obligationto offer their support in turn to help efforts toimprove the economic and political situation ofthe group with which they work.There is an additional ethical obligation which

would occur if the scientific research for which thesamples are needed is likely to produce a "forprofit" product. This concerns justice. Consider ascientific project where three groups collaborate,each bringing something important to the work -one brings the starting material in the form of

208 Indigenous peoples and the morality of the Human Genome Diversity Project

DNA or clones or clinical picture, the second atechnique for analysis, the third an ability to carryout development and patent a product. If there isan outcome, all three groups would expect toshare in it, whether as authors of scientific papers,or shares of research grants, or a proportion ofproduct revenue. It would be unjust if this werenot the case. The indigenous group which is to bestudied for, say, genes which predispose todiabetes regards itself (rightly) as part of thosewho bring essential starting material to the project- their genetic heritage. They have been told thisby the scientists, as the rationale for requestingtheir cooperation in the project. They then findthat everyone else seems to benefit - the scientistsget grants and papers, the biotech companies getpatents and issue shares, and (eventually) the bigpharmaceutical companies may bring out a prod-uct which makes money. What, exactly, flows backto the affected indigenous group? They are stillimpoverished and disenfranchised, and theirhealth status is no better than when they agreed togive the samples. The empowered group uses theknowledge to improve their health, but little ifanything of this benefit comes to those who gavethe raw material used to make the discovery.We know this is oversimplified-in particular,

the commercial significance of a gene discovery iseasily overestimated, and the bulk of the inventiveprocess takes place after the gene analysis.However, from the ethical point ofview it is unjustthat one partner receives so little when its need isso much greater than that of the other partners.We believe that this problem is soluble. The

indigenous group must be taken into the confi-dence of the researchers, and of those who fundthe work. Both the levels of funding and theuncertainties of outcome must be discussed. Thisis not simple, but honest and equal discussion,which may need to take place over time and withpeople who are suspicious due to their experience,is essential. Indigenous peoples who provide keymaterial for a project have a right to share in thelong term profit which accrues from that project'soutcome, even if it is many years in coming. Pro-tocols that outline these principles may be usefulin helping all of those involved to ensure thatissues are fully discussed and understood.

Practical improvements (such as the provisionof a district nursing service to a deprived commu-nity) may be regarded as an embodiment of com-mitment which speaks louder than talk aboutbenefits to humanity. Those in pain often have amore immediate and personal view of benefits to

humanity than others, and ask that such benefitsstart with those in greatest need. Although thisrepresents a breach of the principle that allparticipation in research is strictly voluntary andnot dependent on remuneration, in this contextthe group that has been previously disadvantagedreceives the benefit as a people. This alters theethical dimension as there is no personal gain byan individual.The scientific community should have the

humility to accept that, however good theintentions, the HGDP did not start with the cor-rect approaches to nor respect for indigenouspeoples in many cases. It is the scientific commu-nity that has the ethical obligation to start again,and to offer proper explanations in a context ofrespectful negotiation and a commitment toequality.

AcknowledgmentsPortions of this contribution are based on alecture given to the Human Genetics Society ofAustralasia by Michael Dodson (as Aboriginaland Torres Straits Islander Social Justice Com-missioner of the Human Rights and EqualOpportunities Commission) on "Indigenous So-cial and Ethical Issues: Control of Research andSharing of Benefits", July 1995, in press. Theauthors hope that this article will form part of theongoing process of honest and sincere reconcilia-tion between indigenous people, and newcomersin Australia.

Michael Dodson, BJuris, LLB, PhD, is Director of theIndigenous Law Centre, University of New SouthWales, Sydney, New South Wales, Australia. RobertWilliamson, PhD, FRCPath, FRCP (Edin), is Direc-tor of The Murdoch Institute, Royal Children 's Hospi-tal, Melbourne, Australia.

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