At the brink of the Gene Age
by George T. Javor
A proud father of two fine sons, I occasionally catch myself attributing various traits seen in my boys to either my wife or myself. Their moods come from their mother and their sense of humor from me. No doubt our sons inherited some combination of their parents genetic material, but then, we have inherited our genesgood, bad, or indifferentfrom our parents, they from theirs, and so on.
While there has always been an interest in genetics, in recent years the study of genes seems to dominate all biological sciences.
Genes have also gone public. They play an important role in criminal trials, in identifying persons, in the study of diseases, and in numerous other fields. Every now and then, news reports link a particular gene with a disease, opening up the possibility of arriving at a cure. About two years ago, a gene was implicated in Werners syndrome, a condition in which 20-year-olds get gray hair and come down with ailments common only to the elderly. This gene is thought to be the holy grail of aging research. If the link is right, perhaps there is hope that, like illness, aging may be treated in the future.
The discovery of new genes provides the possibility of eventual cure to genetically caused diseases. As a result we have the Human Genome Project, biologys equivalent of NASAs moon-landing venture. Although this undertaking will cost many millions of dollars each year, the expected results will be as spectacular as the first moon walk, and possibly much more useful. We could be heading for the Gene Age.
Genes: What are they?
But, first, what are genes? What role do they play in the function of organisms?
Genes are segments of chromosomes that produce specific proteins. Each of our 100,000 or so genes contain data for the correct structure of one protein. Our genes are distributed among 23 pairs of chromosomes. A person inherits 23 chromosomes from the mother and 23 from the father; therefore, we have two copies of each of our genes. One exception is the genes found in the male-gender determining chromosomes called Y. Of these, males have only a single copy, and females none.
Both genes and their corresponding proteins may be pictured as strings of beads. The chromosome-beads have four different colors, while the protein-beads have 20. The different colors stand for different chemical structures. The chromosome-beads are called deoxyribonucleotides (abbreviated here as nucleotides) and the protein-beads are amino acids. Three nucleotides in a row on the gene are interpreted by a complex translation machinery within the cell, as a specific amino acid in the corresponding protein. So a stretch of 300 chromosomal beads code for 100 amino acids in the genes protein. Typical proteins may have several hundred amino acids. The sequence of nucleotides in the gene determines the order of amino acids of the protein chain. This is shown in Illustration 1.
Just as spelling affects the meaning of a word, the order of amino acids determines the function of individual proteins. Incorrect spelling of a word may cause loss of meaning. Likewise, the wrong order of amino acids in a protein can result in the loss of its function. The most common reason for the wrong amino acid order is an altered (mutated) gene. A mutated gene keeps directing the production of wrong proteins, and it is often passed on to future generations.
How serious is the problem of having incorrect proteins? The issue becomes critical when we consider the wide range of work these substances do. Every chemical change in the body depends on the presence of specific protein catalysts. Proteins constitute much of the physical infrastructure of living matter. They participate in the transport of oxygen and other nutrients in the blood. The immune system uses protein antibodies in defense against foreign substances. When cells communicate with each other, it is the protein receptors that recognize the chemical signals.
Incorrect proteins cause a hosts of diseases. Until recently, the only recourse doctors and patients had to combat genetically inherited illnesses was damage control; that is, trying to minimize the negative consequences of a faulty protein. In the case of the illness phenylketonuria, for example, the infants ability to metabolize an essential amino acid, phenylalanine, is impaired. The child accumulates toxic substances from this amino acid, resulting in mental retardation. Infants in the United States are routinely tested for this metabolic defect shortly after birth, and if such is found, the babys diet is altered to exclude the harmful amino acid as much as possible. How much nicer it would be if we could correct the genetic defect by either repairing the faulty gene or replacing it with one that functions well.
Breakthrough in genetics
The past two decades have seen a real breakthrough in our ability to deal with genetic material. By the early 1950s it was known that the chemical makeup of the genes was deoxyribonucleic acid or DNA, which consisted of repeating units of four types of nucleotides. If such a structure were represented on paper in a simplified form, using the abbreviations A,T,G, and C for the four nucleotides, we would have one or more books filled with lines similar to this (the order of nucleotides would vary continuously):
-ACTGGTTAGTTCCAGTCAT GAGGTCCAATATAGATCAG TACGATTTAAGGCAT-
This structural monotony prevented scientists from breaking DNA down to smaller, manageable fragments of uniform composition and from determining the order of the nucleotides. The breakthrough came with the discovery of bacterial restriction enzymes. These amazing proteins apparently can recognize short stretches of unique nucleotide sequences of the DNA and break DNA at that point. Therefore, we now have means of obtaining smaller DNA fragments of uniform composition.
Other catalysts (enzymes) were found that could splice broken DNA fragments together. These findings paved the way to where we are todaythe capacity to handle individual genes, to introduce genes of one organism into another, to recombine portions of different genes in the test tube, and to determine the order of their nucleotides.
The Human Genome Project, launched in 1988, is attempting to determine the nucleotide sequences of the 24 human chromosomes (there are two different gender-determining chromosomes called X and Y; males have an X-Y pair, and females an X-X pair besides the 22 other chromosome pairs), estimated to contain about three billion nucleotides and locate the 100,000 genes among these sequences. The nucleotides of the 100,000 genes constitute roughly two percent of the human genetic material. What the other 98 percent of human DNA does is largely unknown. However, because the genes of all humans are relatively similar, the obvious differences between each individual must come from the other 98 percent of the genetic material. One of the factors controlled by these portions of the genetic material is the amount of proteins made. At any rate, it is safe to assume that these non-gene portions are also vital to our welfare.
Order of nucleotides
The exact order of nucleotides of a few less-complicated organisms has already been determined. As of the spring of 1996, the complete sequences of the bacterium Hemophilus influenza (1.8 million nucleotides) and of yeast (13 million nucleotides) have been sequenced. Due to its sheer size, it will be some years before the complete nucleotide order of the human genome will be known.
But whose nucleotide sequence will it be? It so happens that with the exception of identical twins, we differ from each other, on average by one nucleotide per thousand (0.1%) in the non-gene portion of our genome. The Human Genome Project utilizes the genetic material from a comparatively small number of individuals of North-American or European ancestry. This small composite genome will be the first norm to which everyones genome will be compared. It will be a long time before enough genetic testing is done to gain a good understanding of the nature of the variations among human genetic material.
Concerns in genetic studies
There is legitimate concern that the time may come when individuals whose genetic profile fall outside the norm will be considered second-class human beings. Society one day may even decide that people with bad genes are a menace to the long-term welfare of humanity.
Chemical probes already exist to look for genetic signatures of certain gene-connected diseases, such as Alzheimers, or certain forms of breast and colon cancers. Particular aberrant patterns of nucleotide sequences, appear to correlate with an increased risk-factor for those illnesses. For someone possessing such a trait, an advance knowledge of these may provide warning to put preventive measures into practice.
On the other hand, if ones insurance company or if ones employer discovers these risk factors, a person may be in danger of losing health insurance or a job. Such reasons make the privacy of genetic information an important concern. In the name of protecting the welfare of society, how far will outsiders go to intrude upon our most private possession, our genetic make-up? Individuals inheriting disease-causing genes have reasons to be bitter; why should they suffer for no fault of their own? But is it not true that all of us are hostages of our genes? If genes determine our personalities and intelligences, do they not to a large measure control the quality of our lives?
The answer is no. While much of our physical attributes and our basic personality traits are genetically controlled, there is abundant evidence that our environment, lifestyle, and diet are major determinants of our physical and mental welfare. What we read, hear, see, feel, think, and do affect our lives. We have the power to control or modify our moods, thoughts, and actions. We are not static entities; we continually change. As our senses unceasingly sample the environment and report their findings to our central nervous system, moment by moment our brain records the new information and modifies everything else already filed there. The most important point is that our genetic make-up is not altered by what we are storing in our brains. And it is the content of our brains that defines who we are.
Another concern in genetic studies is the assumption in sociobiology that everything that happens in biology is for the benefit of the genome. This theory supposes that genes preceded everything else, and somehow caused the biological world to form for the purpose of maintaining and enhancing the genome. This form of biological determinism helps some scientists to formulate a grand theory of everything, which to them explains why things are the way they are.
Genetic study and evolution
What this and other evolution-based theories do not address is, Where did the information-content of the genome come from? That there is biological information residing in the genome is difficult to deny. It is estimated that one cubic micrometer of DNA can encode 150 megabytes of information. This is 10 orders of magnitude better than current CD-ROMs optical storage capacity. If the complete nucleotide sequence of the common colon bacterium Escherichia coli would be printed in a standard book form, it would be about 3,000 pages long. A similar document containing the information content of the human genome would be a library of 1,000 volumes, each one 3,000 pages in size.
A generation ago evolutionary theoreticians were busy describing a hypothetical primordial, prebiotic world, where the first live organism emerged from non-living components. One of the shortfalls of these chemical evolutionary schemes was the inability to show how nucleic acids could come into existence. The hurdles include the challenge of forming the requisite five-carbon sugar, D-2-deoxyribose in appreciable quantities, the synthesis of the four different deoxyribonucleotides, and their inter-connection into appropriate sequences. But an even more formidable, unsolved challenge for these scientists is to account for the source of biological information, residing in the genome of every organism.
The genome carries direct data for the correct structure of every protein of the organism, and the regulation for the amount and timing of their production. Indirectly, through the actions of proteins, every aspect of the metabolism and infrastructure of the organism is coded into the genome. The level of engineering and biochemical sophistication seen in living matter far exceeds anything seen in our best chemical production plants.
Genetic research: a forbidden area?
Bible believers will quickly recognize the signature on the genome of the same Creator who called into existence the entire universe. But now that we can manipulate genes in the test tube, should we be concerned that we are entering a territory forbidden by the Creator?
If one views the genome as a component of functioning living matter and not some master substance, then the concerns expressed specifically regarding genome research may be broadened to include all biological research. The biblical record quotes the Creator addressing the first humans: Be fruitful and increase in number; fill the earth and subdue it (Genesis. 1:28, NIV). All biological research may fall under the category of subduing the creation, since understanding nature is prerequisite for its efficient utilization.
Genes, in particular, have been manipulated since time immemorial through selective breeding. As long as the new knowledge obtained through research is used to promote health and well being in individuals and groups, we may be sure that it is within biblical parameters. In contrast, research aimed at exploiting biological systems for destructive purposes puts us on a collision course with the Creator. At the brink of the age of genes we face issues not unlike those when we entered the atomic age. The question is, Are we any wiser now?
George T. Javor (Ph.D., Columbia University) teaches biochemistry at Loma Linda University. He has published articles on aspects of the bacterial physiology of the organism Escherichia coli, on biochemical reasons in favor of creationism, and the books Once Upon a Molecule and The Challenge of Cancer. His address: Loma Linda University School of Medicine; Loma Linda, California 92350; U.S.A. E-mail:INTERNET:firstname.lastname@example.org