Editors: Michio Okamoto, M.D., Norio Fujiki, M.D. & Darryl R.J. Macer, Ph.D.
Professor, International Research Center for Japanese Studies
This international project is one of the mega-scientific endeavors comparable to investigations of space, deep-sea, or fundamental elements of the material, which started in this century and will perhaps come into bloom in the 21st century. Since the historical achievement of the elucidation of chemical structure of DNA by James Watson and Francis Crick in 1953, new research field called molecular biology explosively produced researchers who wish to describe life by means of chemical structure of molecules. It also gave birth to the new applied scientific field of biotechnology, which brought about enormous interests in industry. Up to recent times, the main material used in biology were fruit-flies, sea-urchins, mouse and monkeys, by the reason that these are useful in the experiments at the individual level. However, it was only a matter of speculation how far the results obtained in these animals can be applied to human phenomena. Thanks to the techniques developed by molecular biology, it is now possible to examine human genes directly, which resulted in the rapid progress in understanding human diseases including cancer at the molecular level.
Of course, not only in applied biological fields such as medicine and biotechnology, molecular biological techniques have become essential means like computers also in the field of basic biological sciences. For example, evolution of living organisms on which Charles Darwin made theoretical considerations 140 years ago is now a concrete research target feasible to experimental and mathematical investigations by means of molecular evolutionary studies of genes. Through these successes, molecular biologists have become full of confidence in that the chemical structure of DNA decides all the aspects of life: that is the philosophy of the "almighty" DNA. I think the HGP is the symbol of this philosophy. It considers that the quickest way to answer the philosophical question "what is the human" is to decipher all the base sequences of the human DNA.
About ten years ago, the number of human genes sequenced was an order of hundred, and most of them were genes coding for proteins. Today, tens of thousands of genes and the other portions of DNA, that is, the DNA coding for proteins and those not coding for proteins, have been sequenced. According to the recent figure of DNA Data-base of Japan (DDBJ), 33,168 human DNA sequences with a total of 36,674,453 base-pair sequences have been recorded. However, considering the fact that human genome contains DNA of about three billion base-pairs, we have obtained only a handful of ice from an iceberg. If the goal is to read fully a book of nearly 100 pages written by three billion letters, we have so far read only one page of it.
According to an optimistic view, this goal will be reached probably in the first half of 21st century, since the deciphering power of DNA is becoming stronger and the assisting manpower less, year by year, due to the development of automated, high-speed DNA sequencers. However, the problem is not only time, but also the expenses, of course. A simple basis for calculation of one dollar for determination of each base-pair leads to a rough estimate of three billion dollars, or three hundred billion Japanese Yen, but in view of the relating costs and personal expenditures I have not the least idea of the actual expenses. Thus, there is disagreement even among scientists as to whether such a simple labor as to determine the whole base sequences of human genome deserves the time and expenses mentioned above.
An argument may be the following. If all of the three billion base-pair sequences are "true" genes, that is, coding for proteins, the number of human genes must be the order of one million. However, for several reasons, the actual gene number is regarded probably less than 10 per cent of this, namely, less than one hundred thousand. So, why not to decipher these genes only for the time being.
However, the problem is that we do not know what functions the rest of 90 per cent DNA sequences have. It is likely, that there are those DNA segments that regulate the gene activity and even the development of an individual, the mechanism of which is still not understood. Also, there must be a huge amount of "rubbish", or "junk" DNA, originated as the result of evolution of life, reflecting its history of several billion years. Although they may be rubbish, it must be considered that records of whole the evolution of mankind are marked in these DNA sequences. As famous geneticist Dr. Susumu Ohno of City of Hope Medical Center, USA, suggests: "genes never die, but may only "sleep". It is now known that such "sleeping" genes sometimes revive to become active genes during the course of evolution. So, it is not reasonable to consider that the study of junk DNA may be nonsense.
Taken these and other arguments in consideration, it seems to me to be obvious that HGP is practically a reckless attempt. It is true, that the project has been a dream of molecular biologists and its realization hoped for by not only scientists but also industrial communities. However, I do not think this project is fully understood by most people in general. Particularly, they may be bewildered on the moral issues the project innately possesses. However, because of its apparent justice to help understand and treat human diseases, people in general find it difficult to oppose the project.
In addition, such a huge, international research project supported by industrial communities may have potential danger of suppressing tiny basic biological sciences including natural history, the academic value of which is no less than that of molecular biology. Is there any guarantee that the HGP is supported entirely by the independent grants, say, funds raised from industrial communities, separated from the usual budget of governments, universities or other institutions? If, on the contrary, if conventional budgets are used for the project, it is felt uneasy about the disadvantage of scientists who are carrying out more basic and quiet studies than the HGP.
Probably, the HGP underestimates the inconceivable amount of complexity of living organisms which is to be studied separately at different levels such as molecular, cell, tissue, individual and population. Let us imagine that the whole DNA sequences of human genome has been determined. As mentioned above, it is possible that sometime in 21st century the complete sequences of the whole three billion base-pairs written by four kinds of letters, A, G, C, T, are determined. However, this means only that we determine the letters, or the alphabet, if we compare it with language.
Of course, using essentially the same alphabet, English, French or German language has its own specificity determined by the history of human populations. This specificity can not be determined by the alphabet itself, but by words, grammar and rhetoric. In case of the genes, we have now at last attained the technique to read the alphabet. Proteins may correspond to words. We have learned a lot about the tertiary structure and functions of proteins. However, at least in higher organisms including humans, the function to produce the specificity corresponding to the grammar in language is not known. It is not even proven that this function lies in the genome.
So, figuratively speaking, HGP may be compared with a train without destination which has been departed by rather shortsighted decision of some scientists. I can not help imagining that HGP is a modern version of the Tower of Babel. As is well known, this absurd construction work had been started by an order of the king who was tempted to reach the heavens, and failed to continue when people at work could not understand mutually because of language discordance. As to HGP, I doubt that workers are patient enough to be able to maintain the initial hope as long as they like.
2. Human Genome Diversity Project
Besides the questions mentioned above, perhaps a decisive problem has been raised to HGP by anthropologists and anthropology-oriented geneticists. That is the complete ignorance at the initial stage of the project of the fact that the genome has variability both of individual and of populations. At that stage, it was considered that the genome of only a single individual, perhaps an European, was enough to study. Here, again, we see a case of extreme reductionism. I have an impression, or a prejudice one may call, that molecular biologists who are students of chemistry quite often suffer from arrogance and feel not ashamed of their ignorance of biological facts, so much so that their knowledge about humans is, I am afraid, very poor.
Anthropologists know about the evolutionary history of mankind relatively well compared with other scientists. Anthropologists and human geneticists have long studied how each human individual has the genetic specificity different from that of other individual, and how human geographical populations differ genetically from each other. For example, about 30 per cent of our genes coding for proteins are known to be polymorphic, that is, different from person to person. This value is considered to be much higher for the non-coding region, that is, DNA segments not producing proteins. For example, our genome contains the DNAs called "microsatellites" with almost innumerable individual types of molecular repeats, so that this marker is used as "DNA fingerprint" for individual discrimination in forensic science.
Since 1960's, studies of human geographical diversity have been eagerly carried out using new anthropo-genetic methods, replacing old and unfounded classification of races. It is now considered on the basis of genetic and fossil evidences that modern humans originated in Africa relatively recently, say, about 100,000 year ago, and spread to all parts of the world. Also, it is now possible to reconstruct the phylogenetic relationship of major ethnic groups statistically, by using information of the gene. The geographical diversity of human populations is particularly notable in the classic "racial" characteristics such as skin color, hair form and body form. It is now known that to use these variations to classify "races" is erroneous. However, these may provide clues for Darwinian selection, for they may have resulted from genetic adaptation to different environments during the course of human evolution.
Since about five years ago, movements to call for a revision of the initial program of HGP have been put forward, in view of the importance of human individual and geographical variations mentioned above. This proposal is reflected in Human Genome Diversity Project (HGDP). The main advocate is renowned human geneticist Dr. Luigi Luca Cavalli-Sforza of Stanford University, USA, who has recently published a magnificent book entitled "The History and Geography of Human Genes". According to him, it is important as part of HGP to collect a statistically sufficient number of blood samples from various ethnic groups of the world, in order to separate DNA and store cell lines. Since many of the native ethnic groups of the world are now endangered to vanish, it is proposed that this plan should be realized urgently.
Of course, given the long time of perhaps several decades anticipated for a complete determination of DNA sequences of even a single genome, it would be an almost incredible enterprise of perhaps several hundred years if one wishes to decipher all of the sequences of thousands of genomes. So, at present, one may concentrate on collecting and storing samples, as well as carrying out statistical examinations of phylogenetic relationships of various human populations using data of known DNA sequences.
This plan is certainly understandable, so that it is now being examined in detail for realization by the special committee in Human Genome Organization (HUGO). Through such program, our knowledge about the diversity of human genes, both intra- and inter-populations, will be multiplied greatly. This will provide us also with valuable information in understanding the evolutionary history of human species.
However, as an anthropologist, I feel there are certain problems in the movement of the committee mentioned. First, all of the main members are confined to USA and Europe, in contrast to the fact that the objective covers the whole world. Secondly, all the members are human geneticists and no anthropologists are involved, so far as I understand. I will explain in the following why I feel these points are problems.
HGP and, particularly, HGDP are the scientific projects aiming as its final goal at elucidating the nature of mankind. As such, I think, it is not justified for a group of European/American scientists to monopolize the results to be obtained. Also, such projects should start only after sufficient, multidisciplinary examinations of ethical issues, and not start in a hurry by decision by a small number of scientists with limited disciplines, while social understanding is immature. As for ethical issues, opinions of philosophers and ethicists are indispensable, but it should also be realized that for the projects dealing with various ethnic groups of the world one may ask anthropologists. It is not clear to me how much these problems have been recognized by the committee for HGDP. In the following, I will address my personal views on this matter as an anthropologist.
3. The Social Responsibility of Anthropologists
Anthropology is defined as the natural history of the humans. For practical purposes, the study of the humans as organisms and the related species is called physical anthropology, while the study of human cultures and social phenomena is called cultural or social anthropology. The decisive point on which physical anthropology differs from other natural sciences, apart from medicine as applied human biology, is that its direct research object is humans, our own species. In contrast to other animals, human individuals have consciousness and emotion, as well as ability for decision, but are sensitive to discrimination. Human groups are characterized by language, religion, tradition, etc., and the will to belong to a certain ethnicity. Here, laws, ethnic customs and ethnic feelings cultivated by historical events are the elements determining the decision.
What kind of problems are there in carrying out HGDP? The most serious problem may be how to obtain blood samples of native ethnic groups scattered in the world. To study these groups and to conserve DNA and cell samples from these groups are not only urgently needed and important for reconstruction of the evolutionary history of modern humans, but also regarded as an obligation of modern scientific civilization. But how do we give people satisfactory explanation for these purposes, in order to collect blood samples?
Probably, it is the duty of anthropologists to do so. Of course, blood collection itself must be made by medical doctors or nurses, but anthropologists are those who select the ethnic group suitable for genetic study, carry out field studies of culture, demography and ecological factors of that group. Furthermore, it seems to be particularly important for anthropologists to help people understand the objectives of scientific studies. I myself feel through my experiences that this is an extremely difficult task. In the last 30 years, I have carried out a number of field studies including blood collection among Ainu of northern Japan, among Negritos of the Philippines, and among several national minority groups of China.
It was almost impossible to convince people the scientific meaning of blood collection. I have experiences of asking local governmental authorities, teachers, medical doctors or church members to explain to the subjects the scientific importance of our studies. But, frankly speaking, the most successful procedures were medical examination and medication with blood collection, providing big lunch by reason of adding nutrition, and small gifts. Most subjects did not have even the slightest understanding of the research significance, but they often considered our work as a kind of charity. When using the samples thus obtained in my anthropological studies, I have had always a feeling of bad conscience, since my acts could have been ethically criticized as a kind of fraud.
As for a scientist in general, but particularly for an anthropologist, there are two kinds of social responsibility. The first is, of course, to be a good researcher and teacher. Since anthropology is not an applied science with tangible interests to society, a good research should be evaluated by the degree by which it contributes the increment of the scientific knowledge as a culture of mankind. The second social responsibility, I think, is the "accountability", that is, to explain in simple terms to the society in general what is the purpose and the significance of the study. This is not an easy task for scientists busy in writing academic papers and teaching students. However, only by means of such explanation, the understanding of the subjects will potentially be obtained.
As mentioned above, it is difficult to convince the subjects of scientific significance of anthropology. However, through the efforts to explain the public the purpose and its significance to understand mankind itself, the anthropologist will be understood as not being "an agent of imperialism" as some activists claim or a swindler. Only through such efforts, people will eventually understand the significance and the role of anthropology as the science for mankind.