The Human Genome and the Human Genome Project
Humans have about 75,000 different genes. They are made of a chemical known as DNA. Each gene is composed of a string of thousands of modular chemical building molecules, called nucleotides, of which there are four different types. Genes, in turn, are connected by the thousands in bead-like fashion into 23 larger molecular structures known as chromosomes. The set of chromosomes together is known as the "genome." In all, it consists of about 3 billion nucleotides, and every person carries two complete sets - one set received from each parent.
Genes are a type of molecular "code," each specifying a particular biological function. From a chemical point of view, the four different types of nucleotides can occur in any order or number. The way the coding system takes advantage of this is that the particular "sequence" of nucleotides of which a gene is composed determines that gene's function. This sequence is related to the active biological molecules, called proteins, which are specified by that code. If the DNA coding sequence of a gene is altered, it may lead the coded protein to work differently, which can lead to a variety of possible outcomes, including disease.
We have not yet identified all the human genes, but doing so, and understanding how they work can have major importance for humankind. The Human Genome Project is a huge international effort to locate each gene on its respective chromosome and to identify its DNA sequence in some individual, so that its function can be identified. The ultimate biomedical purpose is to enable diseases related to a gene to be understood, but there are other potential benefits: we can learn more about the basic biology of human beings, about out needs for and responses to pharmaceutical agents and nutritional components, and many other socially beneficial application. On Inclusion
The Human Genome Project will characterize "the" human genome in the sense that, with regard to basic function and location of each gene, each person is pretty much alike. But it will be a stereotype of human genes and will result in a composite sequence based on a small number of mainly European families and individuals. These people were chosen more or less by chance to "represent" the human genome, not because of anything particular about their individual biology. since the Human Genome Project is interested in developing this kind of "standard" structure, rather than the study of a particular disease, it does not matter, for the purpose of the Project, which individuals were studied. Knowing the general nature of the structure is what is useful.
However, we know that throughout our entire history each human gene has been highly variable; that is, the details of the DNA sequence of each gene varies among people. This variation arises by a process called "mutation," when a gene is copied incorrectly when it is transmitted from a parent to his or her off-spring. Although the copying mechanism is very accurate, the human genome contains 3 billion nucleotides, and enough mistakes are made each time that we each carry a few DNA sequence variants that our parents did not have. The variant sequences of given gene are called "alleles."
Some alleles have been around for a long time - even as long as our species itself - and are found today in people in most parts of the world. However, every new mutation exists only in on place, and in one person, when it first occurs. Copies of that allele will be passed on to that person's children. For most of human history, the vast majority of people grew up, married, and bore children close to where they were born (transcontinental migration by large numbers of people has occurred only in the past few centuries).
Generally, the frequency and geographic spread of an allele is related to its age. If an allele stays around for a long time, by chance or because it aids its bearers in survival or reproduction, it can increase in frequency and become widespread. At any time, each human population will contain variant alleles of different ages and frequencies. Many alleles will be recent, very localized, and rare. A few will be more common and widespread. Some will be found all across a continent. A few will be found all around the world.
We see this in the variable pattern of genetic susceptibility to diseases around the world. European populations are susceptible to skin cancer when exposed to lots of sunlight, and have high rates of the childhood disease cystic fibrosis, which causes severe breathing and digestive problems, and phenylketonuria, which impairs mental function if untreated. Around the tropical Old World, from Africa to southeast Asia, are found genetic variants that protect somewhat against malaria but also can lead to anemia; the specific variants involved differ within and between the continents. Africans seem particularly susceptible to high blood pressure, and Amerindians and Samoans to adult onset diabetes, apparently for genetic reasons not yet understood.
This reveals a serious potential problem with a genetic stereotype such as that being developed by the Human Genome Project; it is not fully representative of our whole species - it will be most like the sequences in peoples from the same population, although the "standard" genome is, in fact, being assembled by the Genome Project as a composite from several individuals, and is not identical to the sequence of any single person. If we think of humans in terms of this stereotype, it will fail to represent any one person, and will fail more markedly the farther a person's ancestry is away from those mainly Europeans whose DNA was studied.
The need for inclusiveness can be seen in the importance of studying genetic variation related to health. Just like any other variation, alleles associated with disease found in one population may not be found in other populations. Genetic tests for diagnosis, effectiveness of treatment, and prognoses that are based on variation found in one population may be inaccurate in other populations. It is not a sinister act, but the simple fact that most research facilities and funding exist in the wealthier parts of the world means that we will know much more about what makes those people healthy or sick than we know about other peoples of the world. Even within the developed nations, the unevenness of resources may leave some ethnic minorities less well studied, and hence not provided with the same accuracy of effectiveness of health care.
Inclusive thinking is, perhaps, even important in a subjective way. If we think of "the" human genome as found in a composite of individuals mainly of European origin, then each person becomes a variant from that artificial standard, and the less European we are, the more different we will seem. This is wholly inadvertent in terms of the objectives of the Genome Project, but can lead to carelessly thinking that there is a reference human type from which others deviate. Indigenous peoples of the world will immediately recognize this as one of the consequence of a history of colonialism.
Human genes have always varied; they initially all arose by mutation, and they got here today by varying. The study of human genes provides us with a wonderful opportunity to define ourselves at the most fundamental biological level. But we can only do that accurately if we view ourselves as a variable species, the world over. We are not, in face, all variants from some core "type." There is no core type today, and if there ever was one, it appears to have been African, not European. Human Genome diversity Project (HGDP)
A number of geneticists and anthropologists who have always been interested in the worldwide distribution of human variation have reacted to the stereotypical nature of the Human Genome Project by stressing some of these issues about global inclusion. We have argued that variation is as fundamental to the biological nature of human beings as any single gene sequence can be.
To study this aspect of the human genome systematically would require obtaining a sizable random sample of human genes from around the world that would represent variation existing everywhere. Here, "random" and "represent" mean that individuals sampled would be identified because of their location, culture, language, and other traits that should be included in understanding natural human variation. Every person - and his or her unique genotype - around the world would have the same chance to be included in the collection (just as a random sample is needed to reflect public opinion on a political issue; one would not just sample, for example, Democrats to see how the public as a whole feels about an issue).
This idea, still in the planning stage, has been called the Human Genome Diversity Project (HGDP). It is not a formal adjunct of the Human Genome Project (although I think that making it so would be appropriate). In this era of limited funding for science, we do not know what (if any) form an HGDP might take, and of course there will be resistance by competing interests for those funds. One form for the Project would be a bank of genetic material from the sampled populations, deposited in a way that would be accessible to legitimate investigators from around the world.
The sampled individuals would be wholly unidentified to anyone using the data, but the region, language, culture, history and so on of the origin of each sample would be known - as best we can know it - and the results from study of these samples would also be accessible worldwide. The sample would include basically inexhaustible amounts of DNA from tens of hundreds of thousands of individuals, so that studies of many kinds - even ones we cannot imagine today - would be possible. The sample would never have to be re-collected.
The HGDP is not intended as a part of a study of any particular disease (if it were, it would not be a random sample of variation in our species as a whole). But the data would be of biomedical interest because the pattern of variation in and between groups could help us much more quickly find variation in disease, in any local group - by subsequent studies of that disease. Many basic questions about human biology can best be answered with systematic studies of genetic variation.
Since the geographic dispersion of an allele depends on its age in the population, the pattern of variation that we see among populations today can be used to help reconstruct the origins and history of people in all parts of the world. Genetic data can be used to help reconstruct many aspects of human regional history and prehistory, when combined with cultural, linguistic, and archeological data. For example, the continental origins of the people of the island Pacific and Australia might become better known, or the peoples living today in northeast Asia who are most closely related, with native Americans, to their common ancestral population of thousands of years ago, may be identified. The original settlement pattern of the Americas, and the history of the expansion of Bantu language speakers in Africa, or the dual Asian-African origins of the Malagasy people might become better known.
The level of interest in answering such questions from a scientific, rather than spiritual, point of view varies among populations, but it is clearly important to many people around the world. The answers that genetic data can help provide are far from perfect, but we can improve what we know about many important aspects of ourselves and our relationships as people of the same widespread species with this type of data.
Having an HGDP data base would formally establish inclusiveness, whole-species inclusiveness, in the study of human variation from now on. Stereotypical thinking would be reduced, because the population processes described earlier do not produce human beings packaged into fundamentally different groups, but rather, gradual change over geographic space. Perhaps as a result of this understanding, the global investment of research resources for human benefit might become at least somewhat more equitable. Problems
I have painted a positive picture of our collecting and maintaining a data resource on human variation. I think it would be a good thing for the many ethnic groups in the world, and to help build a consensus of inclusiveness among us. But with any global effort, such as the proposed HGDP, there can be problems. It would be native no to recognize that we live in the century that produced the eugenics movement in the western world, and the "scientific" racism of people like Hitler. Or that some people might with to identify, and patent, human genes from any source from which they could get them, for their own personal private gain. And there is widespread suspicion of the potential for science, especially government science, to intrude in peoples' lives - leading to invasion of privacy, or social discrimination against people because of their supposed traits as revealed by genes.
The HGDP did not invent these problems, and indeed the HGDP does not even exist as such - it is just in the planning stage. Gene patenting is going on all over the world right now. Racism exists. Human genes are being sampled on all continents. Detailed genetic "identity cards" may be an unstoppable consequence of technical advances in this area. The HGDP idea arose in the midst of these issues and has become something of a lightening rod for critics of genetics as a result - that criticism is unfair to the HGDP, but perhaps it is good that some project become the focal point for airing the issues and trying to get them settled.
In the first place, there is very widespread and deep misunderstanding of some of the most important of these issues. For example, many people cite the human history of racism, and fear that genetic data could be used by one group to justify oppression of another. Racism asserts that there are differences in the inherent value of human races. Critics of genetics often argue that no "value" can be assigned to genetic variation in this way, and that group differences are trivial, or only pertain to superficial traits like skin color, but not to biologically "important" traits. They feel it would be dangerous to open the genetic box to people who might wish to search for the genes that make one group superior or inferior to another.
But if humans are all of comparable inherent value, what genes do such critics fear we might find? It should be remembered that racism, even "scientific" racism, has existed for a long time and has never actually been based on any specific genes that were shown on make one group better or worse than another. The truth is that we humans are not all the same. We all very, and we very at all genes, not just superficial ones. Groups also vary in terms of the different alleles, and their frequencies, that are found in them. But this has nothing to do with groups varying in quality: we have no evidence for that.
Let us think about whether, in principle, we could assign "value" to genetic variation. It is fashionable to say that this is not possible, that each person is worthy in his or her own way. That is certainly true, overall. But most of us would agree that variation leading to serious disease has negative impact on that person, and it is our compassion that assigns value to this impact - and it is why we spend so much effort to correct such problems. The point is not that some genetic variation exists everywhere, and is characteristic of individuals, not populations. I am not at all concerned that the HGDP would lead to the discovery of genetic variants that could justify racism because I do not believe that such variants exist. That does not mean we should not be on guard against persons who might try to misuse such data to play on peoples' fears for such ends. Skin color, for example, is neither bad nor good, but has been used for or against people politically. It is the use, not the trait, that is the problem.
The organizers of the HGDP, under very important pressure from diverse interest groups, have had to grapple with these potential problems. No two people would agree completely about how to solve these problems, but the proposed project design has already attempted to deal with many of them. One way or another, the problems must be addressed. We can see why this is so by considering the alternative: there is currently no systematic study of human variation that tries to establish international standards for ethics, commercial gain privacy, and proper representation.
There is currently a haphazard collection of genetic material, from samples that are not always properly understood, that can lead to misleading interpretation of human variation - interpretation difficult to criticize if the basic genetic material is not openly accessible and subject or re-analysis. Gene patenting will go on. Ethnic groups continue to be underserved by science. There is little control of discrimination or invasion of privacy.
The HGDP cannot solve all o these problems, which are part of society as a whole, and may not be able to solve any of them completely on a worldwide basis. But, properly done, it can help to limit them and can set an example of high ethical standards in an era not always noted for them. And, above all, the formalized inclusion of human variation, well and properly documented, can give us all, majorities and minorities, worldwide, a better sense that our variation is an essential part of our existence.
Finally genetic data base cannot solve the problem of cultural survival. The HGDP can occur without harming any peoples in any way, and may provide some information they, themselves, may find satisfying. But this is a scientific project with a budget that even in our grander illusions would be trivially small, relative to what would be required to achieve the protection of any of the world's peoples, and that mainly requires political good will in any case. We cannot, and do not, think for a moment that the HGDP is a substitute for efforts to protect and enhance human populations everywhere, no matter how small or economically disadvantaged. At most, we can hope that it would raise awareness, help distribute scientific technology and, hence, scientific power, and could help modify the harshness with which people can think of each other.
From my personal perspective, I believe that a beneficial data base on human variation can be created if several things are a part of it: The agenda for sampling must be open, and modifiable by input from the lay as well as scientific public. Those in control of the data base must have a rotating membership, so on closed group or outlook can become a fixed part of the Project. There must be close, external scrutiny - from groups like Cultural Survival - to ensure continually that the data base is not abused. Access to the data must be open, so that those who disagree with analysis that is done on the data can re-analyze the date themselves.
Many of these attributes are being included in the HGDP planning. To paraphrase the objectives of Cultural Survival, the organizers of the HGDP insist that biological differences are inherent in humanity; understanding this human diversity enriches our common earth. Article copyright Cultural Survival, Inc.
