DNA and the goal of human perfectibility - genetic engineering in human beings

DNA AND THE GOAL OF HUMAN PERFECTIBILITY

Science has a peculiar status in modern society. Its institutions and practitioners are widely perceived as being neutral, objective, value free, above mere human politics. Yet this is far from being the case. The history of science, its errors as well as its successes, its peculiar obsessions and its ideological role as a legitimator of the social order, cannot be understood unless we recognize that scientists can only approach the world in ways which are shaped by their own class perspectives and their assumptions as predominantly white males in a racist and patriarchal society. This is not to say that knowledge about the material world cannot be obtained or is entirely subjective, but that there is a constant dielectric between the scientist as a social being, living and working in a particular historical conjuncture, and the material reality of the world being studied.

This is nowhere better illustrated than in current debates within and about biology. Ever since the publication of Darwin's The Origin of Species in 1859, biological questions have been coupled with those about human society, and the mix has been explosive. Political and philosophical questions about the biological limits to possible human societies, the nature of human nature, the distinction between human and other animals, and the extent to which human evolution could and should be directed by conscious intervention have bubbled up in the form of social Darwinism in the late nineteenth century, and the eugenics movement that peaked in the 1920s and 1930s. Within the past decade a host of influential books have reasserted the claims of biological determinism that capitalism, aggression, racism, patriarchy, and xenophobia are human universals, the inevitable products of evolutionary history; and that human differences in intelligence, ability, susceptibility to mental disorder, and even criminality are the result of genetic predispositions. This modern version of biology as destiny, which goes under the rubric of sociobiology, has provided ideological legitimation for the New Right and neoconservatives' insistence that our unjust society, divided by class, race, and gender, is in some way forced upon us by our biology.

Along with claims for the fixity of human nature have come the new technologies of genetic engineering and in vitro fertilization. These techniques seem to offer the possibility of tampering with that fixed human nature, of opening once again the prospect--so popular in the 1930s but without the techniques (other than those of the Nazis, of course)!--of eugenic improvement of the human stock.

The claims and aspirations of this new biology are not new but go back to the origins of modern biological theory, and to central ideas about human development and evolution. The term "evolution" has been applied both to the process of transformation of species over geological time, and to the transition of an individual organism from embryo to adult, a process today called development. Important conceptual issues are at stake in the similarities and dissimilarities between these two processes, whose exploration lies at the center of biological endeavor. It is necessary to come to terms with both development and evolution in order to understand why biological determinist models of human nature are essentially ideological rather than scientific, and the limits to the technology of human perfectibility offered by genetic engineering.

Genotype and Phenotype

The central problem of genetics has been how "like begets like," how a fully formed organism can develop from the fusion of sperm and egg. Sperm and egg mainly contain giant molecules of the substance DNA (deoxyribonucleic acid). The DNA molecule is composed of a series of units (nucleotides) arranged in a precise sequence. Some parts of this sequence serve as a code which can, under the right biological conditions, be translated into sequences of a different unit, amino acids, which form the building blocks of proteins. Proteins help shape all aspects of the organism, from the structure of individual cells and organs to the complex metabolic processes by which organisms survive, grow, and develop. It was immediately apparent, from the moment in 1953 when Crick and Watson showed that DNA consisted not of a single strand of nucleotides but of two complementary strands wrapped around each other in the famous double helix, that DNA molecules could themselves be copied by unwinding the strands and using one as a "template" on which to copy a new version of the other.

For Crick, Watson, and the generations of molecular biologists that followed them, the central problem of genetics was solved. Because DNA provided a code for the making of proteins, development consisted of the orderly "readout" of this code; because DNA was self-copying, genetic transmission meant merely the passing of a DNA "program" from parent to offspring. (The computer terminology beloved of molecular biology is not coincidental; it is a part of a consistent process whereby biologists attempt to reduce the complexity of living organisms to the relative simplicity of human artifacts). The myriad interacting processes of development became reduced to a simple, linear flow of information from individual sequences of DNA--that is, individual genes--to protein. Crick called this the "central dogma" of molecular biology. DNA became a "master molecule," the organism's genotype, containing all the instructions necessary for its life's pattern, and uniquely capable of determining the organism's phenotype--that is, its outward form and properties as an individual living creature. For such a reductionist approach, everything, from the color of our eyes, to why we do what we do, to why and how we have evolved, is embedded in DNA. Indeed, for sociobiologists who have followed in molecular biology's footsteps, organisms themselves have become nothing but DNA's way of making more DNA.

But it has become increasingly clear, even to the most reductionist of molecular biologists, that there is something fundamentally at fault with this logic. First, it turns out that only a small portion of the cell's DNA is actually involved in making proteins--perhaps 1 percent in all. The function of much of the rest is unknown (molecular biologists, embarrassed by this, give this residual 99 percent various names, from repetitive DNA to junk DNA to selfish DNA!). Even this figure of 1 percent may be misleading; it will code for some 100,000 different proteins, but not all of these are made in all cells at all times. As embryo grows to infant and infant grows to adult, the production of particular proteins in particular cells is switched on and off in an intricately ordered sequence. For instance, at birth and during weaning, all human babies produce an enzyme in their gut, lactase, which enables them to digest the milk sugar lactose. After weaning, most human populations (except Caucasians) cease to drink milk, and production of the enzyme ceases.

In general, varying amounts of DNA are being used in the production of proteins at any one time and in any one cell. Thus at any one time the outward form of an organism, its phenotype, is the result of the changing production of proteins from DNA in a particular series of changing environments.

Genes and Environment: The Lesson of Phenylketonuria

It is the interaction of DNA with environment during development that makes absurd the simple linear sequence beloved of reductionist molecular biology, which claims that genes, the DNA molecules, are in control and determine an organism's fate, while the environment merely provides a passive medium in which the strategy of the genes is played out. Reductionist molecular biology of this sort misses the essentially dialectical nature of the interaction of gene and environment during development.

How do genes and environment interrelate during the development of the organism? Ever since its nineteenth-century origins, genetics as a science has had difficulty in dealing with the concept of the organism as an integral unit. To cope with this, the organism is decomposed into a set of more-or-less arbitrarily defined "characters" (like eye or hair color, or the ability to roll one's tongue, or, for some, intelligence or criminality). According to this conception, genes and environment produce these "characters" by some simple additive action.

There are many reasons why this simple additive model is inadequate. First, just as all individuals (except identical twins) are unique genetically, all individuals (including identical twins) have unique environments. Second, the concept of the environment must be understood at many levels. To a gene, all other constituents of the cell, including the proteins, are part of its enviornment; since proteins are themselves gene products, this means that each gene has all other genes as part of its environment. The cell itself has an environment, which is contributed to by all other cells in the body; cells influence one another by producing hormones and other signalling substances. And the organism has an environment which includes not merely the physical world but the biological and social worlds as well. Because environment is multileveled and constantly in flux, the relationship of gene and environment is never simply additive, but much more complexly interactive.

This is why we can only speak of the function or expression of a gene if the environment is also defined. Although geneticists often talk of genes "for" eye color, or diseases like sickle cell anemia or phenylketonuria (PKU), this shorthand is misleading. In the genetic disease PKU, which affects 1 in every 10,000 children born in the United Kingdom or the United States, the affected person lacks a gene responsible for coding for a particular protein, an enzyme necessary to metabolize (break down or utilize) a normal dietary component, the amino acid phenylalanine. In effect the gene "for" PKU means the absence of the gene for the phenylalanine metabolizing enzyme. The child with PKU, if untreated, will develop a variety of deficiencies in many body tissues, of which the most striking is mental retardation. The effects of the missing enzyme are different in different body organs and depend on all the other properties and functions of that particular organ--that is, on the immediate cellular environment of the gene. Incidentally, just why one effect of PKU should be mental retardation is unknown despite detailed knowledge of the genetics and biochemistry of the condition--a good example of the difficulty reductionist biology still has in predicting the properties of an organism from knowledge of its constituents.

But the key to PKU is the phrase in the preceding paragraph "if untreated." If the condition is detected at birth, it can be rectified by providing the child with a diet free of phenylalanine (the amino acid which he or she cannot metabolize). In an environment free of phenylalanine, the gene "for" PKU, though still present, no longer produces mental retardation. In other words, the same gene in different environments produces different effects on an organism. Furthermore, the child with PKU is then virtually indistinguishable from other ("normal") children. Thus different genes, in different environments, may produce the same phenotype.

Given such complexities, it is scarcely surprising that we understand neither the rules by which genotypes are translated into phenotypes nor how a change in genotype affects phenotype, despite a clear knowledge of how DNA is translated into proteins. This is why we should be skeptical of claims that it is possible to measure the genetic contribution to such complex expressions of human social interactions as intelligence or criminality.

Reductionist molecular biology remains convinced that there will come a time when, given a DNA sequence and a specified environment, they will be able to predict the phenotype of the organism. Other biologists are less certain. It is a striking fact that although humans and chimpanzees have some 99 percent of their DNA sequences in common, no one would mistake a chimpanzee phenotype for a human. At present we have no idea what might be embedded in the residual 1 percent of DNA that makes the difference between humans and chimpanzees--or, indeed, if we ought to be looking at a different level of biological organization to account for these differences.

So far I have been discussing DNA in relation to one of its two roles, that of development. When Darwin formulated his theory of evolution by natural selection, neither the general rules nor the molecular mechanisms of heredity were understood. Darwin's theory was the logical consequence of two irrefutable premises. First, like begets like (with variations); second, all living organisms can produce more offspring than survive to reproduce in their turn. As survival or nonsurvival is not entirely due to chance, it follows tht those more fit for (or as is now said, better adapted to) their environment are more likely to survive to reproduce in turn. Hence more favorable variations tend to be preserved and species evolve (change) as a result of this process of natural selection.

What has DNA to do with this? The synthesis of genetics and Darwinism which developed from the 1930s on argues that precise changes in DNA, occurring as a result of random mutations and other internal molecular rearrangements, produce variations between offspring on which natural selection can act. Just as molecular biology sees the fixed sequence of DNA as determining the phenotype during development, so it sees changes in DNA as the sole cause of changes in phenotypes during evolution.

There remain a number of conceptual issues which divide evolutionary biologists and about which passions run high. Except for the creationists, no one doubts that evolution has occurred; and the debates are mainly about the mechanisms of change. Expressed in the bald form offered above, natural selection theory seems obvious and incontrovertible. Yet while it provides a good explanation of how species get better at doing what they do, it provides a poor and stumbling explanation of how new species emerge. But here my main concern is with the concept of adaptation or fitness, and whether it is appropriate to argue, as does reductionist molecular biology, that all selection ultimately occurs at the level of the gene.

The concept of fitness cannot be absolute; it must depend on the environment. For instance, in modern Western societies the gene responsible for sickle cell anemia is a deleterious mutation; carriers (that is, those who inherit one copy of the "sickle" gene and one of the "normal" gene) are at some minimal disadvantages and those who inherit two copies of the "sickle" gene, one from each parent, are likely to have a short life. So why has the trait not been eliminated during human evolution? The answer generally given is that having one sickle cell gene confers some immunity from malaria, and hence in malarial regions is an advantage.

While the gene "for" sickle cell was advantageous when malaria was prevalent and has become deleterious due to the changing environment, other genes which were previously disadvantageous have ceased to affect fitness. As Darwin's ideas became accepted during the first part of this century, concern began to grow that industrialization, health care, and social amelioration were preserving certain human traits which would otherwise have been eliminated--for instance, a genetic propensity to shortsightedness. Eugenicists began to worry about genetic deterioration, the prospect of an increasing "genetic load" of deleterious genes. Such an argument ignores the fact that the modern human environment includes spectacles. One consequence of a genotype that can participate in making a society which can produce spectacles is to change the environment such that genes "for" shortsightedness are no longer less fit than genes "for" 20/20 vision.

This points to a further complexity in the use of the term "environment." Developmental biology has tended to see the environment as a fixed background against which the internal genetic program of the organism unrolls. Evolutionary biology has tended to see organisms as passive recipients of an environment that presents them with challenges which they either pass or fail, depending on their genes. Both metaphors ignore the active part which any organism plays in changing and transforming its own environment. Put a bacterium into a glass of water and add a drop of glucose and the bacterium will swim toward the glucose, seeking a glucose-rich environment. It will metabolize the glucose, taking some into itself, and excrete waste products, including acids, which will change the environment. Eventually the bacterium will move away from the now acidic environment. All organisms, even the simplest, actively seek, interpenetrate with, and transform their environment. Humans do so consciously. This is one of the senses in which we can say that we make our own history, though not in circumstances of our own choosing. And it is one of the reasons why a knowledge of the evolutionary or historical past does not allow us to predict the course of the evolutionary or historical future.

A further problem with the idea of fitness is deciding which aspect of a phenotype selection might be acting on. The past few years have seen a host of evolutionary fables being produced to "account for" particular presumed phenotypes, from the shape of the human chin to children's allege dislike of spinach. To give an example, hemoglobin is characterized by its red color. Is its redness a phenotype which has been selected for? A story could be constructed about how red acted as a warning signal and hence registered danger, alerting individuals close to a wounded victim of the need to escape. Yet it is much more likely that the red color of hemoglobin is a contingent property, a consequence of the fact that iron-containing compounds are red. What has been selected for in hemoglobin is a molecule with very high oxygen-carrying capacities. Red may then have become a warning color because blood was red.

Programmed by Our Genes?

Some molecular biologists, and following them sociobiologists, have argued that all selection acts ultimately at the level of DNA. This has led to such extravagant claims as that an organism is "merely" DNA's way of creating more DNA or that human beings are "lumbering robots programmed by our genes," to quote Richard Dawkins, author of The Selfish Gene. However, just as "the environment" is multilevelled, so too must selection act at a multitude of levels.

One individual length of DNA, or gene, because it codes for a more effective protein for a particular cellular task than does another slightly different piece of DNA, may be more likely to be favored in natural selection. As I have emphasized, however, the environment in which any gene acts includes all the other genes in the cell. "Selfish DNA" theory assumes each gene is an isolated monad, competing in the marketplace against all others, like perfectly competitive capitalist producers. This theory thus ignores the fact that survival of any individual gene may require cooperation with other genes in the same cell. Hence another "level" of selection involves the "genotype" as a unit. Further, the genotype itself exists within an organism whose survival depends on its interaction with others. Hence it will only be selected for in the context of the entire population of which it is a part. In the long run, therefore, natural selection occurs at the level of the population, not just the individual. Finally, if a "fitter" species evolves, an entire population may be eliminated irrespective of the selective advantage of particular genes or individuals.

These points are important because much attention has focused on the question of the evolution and genetic determination not merely of the biology of the individual but of complex social behavior. For sociobiology, such behaviors as, for instance, selection of a mate, are regarded as "phenotypes" which are determined by genes. But why does behavior which is apparently disadvantageous to the organism evolve? One bird in a flock may give a warning cry at the approach of a predator, drawing attention to itself but potentially saving its fellows. How can such apparent altruism be a product of "selfish DNA"? The answer popularized today by sociobiology is that by potentially sacrificing itself, the bird may preserve its close relatives, which share some of its genes. Such behavior is said to be in the "interests of the genes," if not of the individual. Despite a host of more or less vulgar popularizations of this idea, its relevance to the human situation (and indeed to most animal behavior) remains at best obscure.

Improving Humans

Let me try to pull these threads together in the context of human evolution. It is sometimes argued that, with the arrival of homo sapiens, biological evolution was replaced by "social evolution." However, the analogy is not helpful. Evolution in the biological sense is an inevitable consequence of being alive, irrespective of disputes over details of its mechanism. But the processes of change in human socieities are not comparable with the process of natural selection; they do not involve self-replication of molecules or organisms. Social change results from the interaction of biological, economic, and cultural forces and conscious actions, which need to be studied in their own terms, not by spurious analogy. It has also become fashionable among some biologists and New Right political philosophers to argue that human societies are the inevitable products of the properties of self-replicating genes; selfish genes make selfish people and hence, although we may not live in the best of all conceivable societies, we live in the best of all possible ones.

Such claims are as fallacious as were those of an earlier 1930s generation of eugenicists and political theorists. We do not know and cannot predict the limits of human nature set by the human genome. The sorts of societies we build and the ways in which we view the world are of course shaped by our biological natures. The human genome ensures that we live for a maximum of a hundred years or so, are bipedal, have language, and are around 1.5-2.0 meters in height; that we can see the world through eyes sensitive only to radiation of a small range of wavelengths; that we cannot sprout wings and fly (though some of these limits, such as that which stops us becoming angels, are set by structural considerations rather than DNA). If we were only a few centimeters in height, or could see in the infrared or ultraviolet wavelengths, or fly like a bird, we would perceive the world differently and build different societies. But the extraordinary thing about the human genome is that it permits us to build instruments which enable us to sense wavelengths that the eyes cannot reach and build machines that allow each and every one of us to fly without becoming an angel. Such societies, such machines, do not go against human nature, for there can be no such antithesis. It is the human genome which makes possible the brain, language, social and tool-using ability that enable us to create our own history. It is our genome, therefore, which allows us--which almost insists--that we constantly transcend the limits apparently set by that very genome, enabling us to continuously reconstruct our future on the basis of our past, to have the freedom to make our own history.

The Future

The new genetic knowledge is part of the process of making that history. Saying this is not to embrace a naive progressivism. Still less is it to accept that a science which is not controlled by--is not in the hands of--the people can automatically be beneficial. Knowledge in the hands of the dominant class, race, and gender is knowledge used in support of that domination. Nonetheless, one is entitled to ask what scope this new knowledge offers for changing the future pattern of human society or human evolution.

As to changing the pattern of society, my answer must be "not much." The social relations of human societies are likely to be changed more by social, economic, and political actions than by knowledge of DNA. As to human evolution, the air is certainly thick with promises--or threats. Both positive and negative eugenics are again in discussion. On the one hand, sperm banks are being created to preserve the offerings of males perceived as especially gifted, such as what was to be called the "Herman J. Muller genetic repository" in California until his widow protested. On the other hand, parents can now use amniocentesis, and in time possibly gene therapy to detect or replace particular disordered genes in the fetus.

Such possibilities have led to wide debate, especially centered on the morality of genetic engineering, in vitro fertilization (IVF), and related techniques. To me, the question has always seemed wrongly posed, for it endeavors to turn issues of priority in health care into those of abstract ethics. Rather one should ask the prior question, which IVF is presumably designed to help answer: how can we increase the number of wanted, healthy babies? What prevents wanted, healthy babies from surviving? In Britain, the perinatal mortality rate--that is, the number of babies dying at or just after birth--is several times higher if the mother is poor or in the manual working class than if she is wealthy or upper middle class. If we want to save babies, we can do so best by applying known social, economic, and health care improvements to the deprived classes. The language of priorities says that we should not get excited about new techniques like IVF until we have addressed the question of how we save babies who die from lack of application of simple preventive and health-care measures.

Nonetheless, as a way of circumventing infertility the techniques of IVF are here to stay, though their contribution to human evolution is likely to be marginal. Nor, despite science fiction speculations about the prospect, is the cloning of humans likely to prove technically possible in the near future. Philosophical speculations about the implications of such procedures will doubtless continue to fascinate, but our "brave new world" is unlikely to be that envisaged by Aldous Huxley.

In fact, the limits to the prospects of gene manipulation are likely to be set more by theory than by techniques, and were foreseen as long ago as 1930 by Muller, Haldane, and other geneticists. First, most phenotypic conditions of medical or social interest are the products of multiple gene interactions, whose outcome depends on the environment. It will be easy to predict the hair or eye color of the offspring sired by a Nobel Prize winner's deep-frozen sperm; we have no idea about which of many different multiple sets of genes, in which of an almost infinitely varying set of enviornments, might be associated with intelligence, even assuming that the term "intelligence" represents a measurable phenotype. Put crudely, we do not know what to brred for, but we can make a fairly good guess as to the sorts of environment to avoid if we wish to improve the chances that a child with any old genotype could become a potential Nobel laureate.

On the side of negative eugenics, there are several single gene disorders, where amniocentesis and genetic counselling can provide advice today and perhaps worthwhile gene therapy tomorrow. Huntington's chorea, muscular dystrophy, and some blood diseases are often quoted. But it should be emphasized again that the overwhelming majority of diseases and distresses from which humans suffer cannot be traced to specific genetic components (that is, no particular genotype predisposes a person to the disease). Even for most diseases thought to have a "genetic component" (like heart attacks), the genetic contribution is multiple and diffuse, beyond the useful scope of even speculative therapy, and would continue to be even if the long chain of mediations between genotype and phenotype discussed above were more fully understood.

Nonetheless, the new technologies do raise questions that go beyond issues of priority in resource allocation. As in all areas of our social existence, they confront us with questions of control and power.

COPYRIGHT 1986 Monthly Review Foundation, Inc.
COPYRIGHT 2004 Gale Group