Editors: Norio Fujiki, M.D. & Darryl R.J. Macer, Ph.D.
Professor, Division of Genetic Medicine, California Pacific Medical Center, USA
Historically, human genetics has been a field concerned with identifying variable human phenotypes and then explaining the variance by the action of genes. Traits or diseases were noted, pedigrees and twin pairs studied, segregation consistent with monogenic inheritance sought and occasionally linkage established (most easily for genes on the X chromosome). The biochemical basis for the genetic control of a few traits was known before the gene itself was analyzed.
With the advent of new techniques to reproduce, sequence and manipulate human DNA, the study of human genetics has become the elucidation of the human DNA sequence and the location of the functioning genes within this code. Since the physiological mechanisms underlying most simple genetic traits are unknown, strategies locating the gene, describing its sequence, inferring its product and then studying the putative protein's functional role (reverse genetics) have been utilized.
Traits which are clearly polygenically influenced or where little evidence supports a major genetic impact on phenotypic variance may be approached by DNA based methods. The results of this revolution in technical abilities have been both an explosion in our knowledge of the position and action of many genes, and the unfortunate belief that all important human variation is genetically based and analyzable by techniques using DNA. The fact is that though DNA techniques can give basic information about the genetic component of simple and complex traits, the reconstruction of the causation of these characteristics from basic genetic elements is slow, can be incomplete and may in some cases be untenable and wrong. Socially unacceptable consequences have arisen when genetic approaches to human biology have underemphasized environmental causation or stimulated inappropriate responses to supposed biological (genetic) conditions.
The Human Genome Initiative (also known has the Human Genome Project HGI) is a international effort to coordinate and speed the analysis of human DNA. Its goals are to sequence the entire human genome (approximately 3 billion DNA bases in haploid content), locate all the genes within this sequence (about 100 thousand in number) and develop tools and methods for deriving useful biological/medical information from the mapping and sequencing of genes. In addition, HGI has recognized to some extent that the approaches and information it generates may produce or exacerbate important ethical, legal and social issues. It therefore will appropriate approximately 100 million dollars to study, and potentially make policy recommendations concerning, the application of human genomic knowledge (the ELSI Program). The relationship of the ELSI Program to the basic science effort and its enormous size, make it a truly unique innovation in modern science.
HGI has been underway for several years in a few countries, has received considerable attention and funding in the United States and the United Kingdom, and has fostered the International Human Genome Organization (HUGO). Many other countries have expressed support for HGI though for political, economic or cultural reasons have not devoted significant funding for its research. There remains objections within the scientific community to the expansion of human genetics, the "Big Science" approach adopted by HGI and its initial research programs. In addition, to the extent that HGI promotes biological reductionism, genetic determinism and attempts to manipulate the human germline, it will continue to generate considerable controversy and resistance within and outside of science and medicine.
Despite these objections, HGI has flourished in the United States. HGI supported researchers continue to develop new techniques for mapping and sequencing DNA, and find genes associated with important human traits or diseases at a dizzying rate. The project's funding has increased substantially over the last 3 years despite an economic slowdown in the United States and large federal budget deficits. The reasons for this political and economic success include: the apparent scientific progress attributable to the application of genetic approaches; the influence of the biotechnology sector in promoting, conducting and utilizing HGI programs (it should not be forgotten that HGI was originally proposed to be a private business by Nobel laureate Walter Gilbert); the benefits of large scientific projects for certain U.S. Federal agencies and the economy; and the timeless attraction of biological explanations and alleviations of aspects of the human condition (eugenics). The attractiveness of eugenics, understanding heredity and escaping its constraints on a scale greater than just individual insight and change, has always been notable to Americans. In fact, the current ascendancy of human genetics in the scientific community is highly reminiscent of conditions during the 1930's, except that the reliability of the scientific data being generated is considerably improved.
To conclude this section, the origins of HGI can be found in the turn to genetic methods to study human biology over the last 25 years and the eugenics movement, which hopes to apply these techniques (and later treatments) to a broad range of human traits and problems. The likely results of HGI will be the successful genetic analysis of simple human traits and illnesses, the expansion of commercialization of human biology and genetics, and problems inherent in applying eugenic approaches to personal and social issues.
One of the eugenic results of the expansion and misapplication of human genetics is genetic discrimination. It is most simply defined as discrimination, prejudice and stigma arising from knowledge or study of genetic information. It differs from other forms of discrimination based on race, gender, ethnicity, religion or physical characteristics in that it can have no physical manifestations, affects family units and reproductive options, and usually elicits stereotypic responses including genetic determinism and inevitability.
By studying the eugenics movement and current manifestations of genetic discrimination in the United States, the conditions necessary to produce genetic discrimination can be gleaned. These include:
1. Available genetic information or pseudo-information.
2. Hereditary anxieties.
3. Acceptance of genetic myths (reductionism and determinism) by important groups in society.
4. A society which responds to other aspects of human difference with stigmas, prejudices, discrimination and racism.
Earlier in this century, the impulse to discriminate on genetic grounds stimulated groups to claim hereditary privileges and engendered laws restricting reproduction, limiting immigration or forcing sterilization, and the Holocaust. Though political and judicial decisions affecting reproduction by sterilization, justified on genetic grounds, still occur in some countries, subtler forms of genetic discrimination have appeared particularly in the United States. These include discrimination in access to:
3. social entitlements like insurances.
5. governmental services.
Since limiting access to healthcare enhances the mortality rate from many treatable illnesses, genetic discrimination in the United States currently has the same fatal results as the more direct pogroms promulgated during the Third Reich in Germany. The use of genetic information to identify and stratify groups, and to deny them social entitlements and civil rights, is also identical to patterns described during previous periods when eugenics was popular. What is different is that current programs are based on somewhat more reliable scientific evidence and there may be less political will to identify genetic discrimination as wrong and put an end to it.
The United States is currently the major producer of new genetic information, is investing heavily in HGI and may have the highest prevalence of genetic discrimination among the developed countries (this is excluding many less developed countries with overt racist governments and is primarily a result of the healthcare access system in the United States). Since international cooperation is a goal of HGI, it seems reasonable to expect that access to information and techniques produced in the United States may lead to an export of genetic discrimination as well.
Which are the countries which are most likely to import genetic discrimination? First, it will generally be wealthy countries who can afford to apply expensive genetic techniques and develop a scientific program in human genetics. Genetic discrimination requires the establishment of a scientific or pseudo-scientific establishment in order to generate and store the data.
Second, countries with a history of involvement in eugenics will be likely sites. There is no evidence that the groups who previously embraced this worldview have renounced it, and in many countries, these political elements have renewed popularity and power.
Third, countries who currently manifest racist and discriminatory policies towards intranational minorities or international groups will likely adopt genetic discrimination to isolate these groups as well. This is consistent with the hypothesis that genetic discrimination arises from the same impulses as other forms of discriminatory personal and social behavior. It also recognizes that as HGI progresses, genetic discrimination may become more internationally acceptable as a byproduct of human genetic scientific progress (a concept sometimes euphemistically termed "appropriate discrimination").
Finally, countries with little or no tradition of acceptance of ethnic or cultural diversity, and without a legal tradition which clearly protects the rights and privileges of minorities, will see a rise in genetic discrimination. Countries who do not recognize the need to care for and assimilate those with disabilities will be particularly susceptible to this outcome. In those countries where pluralism is not considered a social, political and cultural benefit, genetic information will produce further criteria for disintegration, segregation and isolation unless an effective legal and public policy response is already in place to limit this effect.
Given current international political conditions and the history of eugenics, it is difficult to be optimistic about the final results of HGI. It is likely that many individuals will be hurt by the misuse of their genetic information by others. It is just as likely that genetic information will be misused to explain social, political and cultural problems, and to justify political power structures which emphasize inequality of citizens or groups. To prevent this unfortunate outcome of HGI, there will need to be a new era of international cooperation and agreement probably lead by the scientific community who should be able to best articulate the limitations of the scientific progress associated with HGI. HUGO and other international scientific and biomedical organizations should adopt a binding set of principles to include:
1. A rejection of the use of genetic information to limit civil rights, to violate privacy and dignity, to deny entitlements and to justify social or political inequality. This should be coupled with a positive endorsement of the inherent equality of all humans, and the national and international benefits of human genetic diversity.
2. An enforceable ban on collaborations and information/ technology transfer to countries who do not endorse human equality arising from genetic diversity, and who demonstrate that HGI generated information will likely be used for the purposes of genetic discrimination.
HGI can produce scientific progress which can reduce the suffering of those with hereditary disorders, and enlighten the study of a broad range of human traits. To insure this salutary outcome, the scientific community given its great prestige and power at the end of the twentieth century, needs to play a leading role. It should assert that scientific results do not provide a justification for genetic discrimination, and that human diversity and rights are inherent conditions which need to be protected and respected.